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Analysis of the findings of the 1997 National Survey found that over a quarter of the men who had used heroin reported first initiating use in prison buy 150 mg zantac free shipping gastritis tums. Care planning is integral to the process; this is an agreed plan of action between the service user and the Criminal Justice Intervention Team worker buy zantac 300mg free shipping gastritis diet honey, which involves setting goals based on the individual needs identified order 150 mg zantac free shipping chronic gastritis histology. This plan documents and enables routine review of the service user’s needs, goals and progress across four key domains: • drug and alcohol use • physical and psychosocial health • offending • social functioning (including housing, employment and relationships). The different levels/tiers of treatment reflected their intensity and ranged from non-specialist general healthcare through open drugs treatment and community-based drug treatment to residential drug treatment. This requirement is one of a menu of 12 requirements to which offenders can be sentenced. There are three levels of intensity of contact, which include, but do not entirely consist of, medical treatment. Before making the requirement, the court must be satisfied that: • the offender is dependent on or has a propensity to use any controlled drug • he or she would benefit from treatment • the necessary arrangements can be made for the treatment • the offender agrees to comply with the requirement. Arrangements for treatment are available through the Probation Trusts, which operate at a local level. There is provision for the court to review the progress of the offender during the order, and to agree changes in the treatment. The treatment can be residential or non-residential, which is decided by the court, and must be supervised by a suitably qualified person. A review of the National Drug Rehabilitation Requirement found a variation in treatment delivery across England and Wales. Sessions were set aside in existing magistrates’ courts for dedicated panels of magistrates or particular district judges to sit for sentencing. Appropriate sanctions and other rehabilitation services that could be included in community sentences were available to all courts in England and Wales. In January 2011, the Ministry of Justice published The Dedicated Drug Courts Pilot Evaluation Process Study. It also leads to a blurring of the distinction between judicial and therapeutic strategies, with the result that a drug user may view the doctor treating them as part of the judicial system and be confused about whether they are being punished, or treated as a patient. Effective communication is essential to ensure that those undergoing treatment fully understand their rights as outlined in Section 10. Issues that arise for health professionals include the following: • high rates of illiteracy and learning disability in offenders, often coupled with a lack of time and/or privacy for consultations, which raise serious questions about their freedom to give informed consent • the perception of offenders that the doctor is not impartial but is working for the police or prison • the ethics of providing treatment when the patient has effectively been coerced to consent. It has been estimated that the value of illicit drugs within prison is about £100 million. There is disagreement as to which of the routes of illicit supply is the most prominent. A Policy Exchange report in 2010 contends that the majority of drug dealing within prison is highly organised and involves the collusion of around 1,000 corrupt staff, which equates to around seven prison officers per prison. It is important that medical professionals are able to make independent clinical and ethical decisions about the most appropriate treatment for individuals in prison, in exactly the same way as for those living in the community outside prison. Treatment with methadone in prison has been shown to significantly reduce heroin use among those treated. Treatment options will include continued opioid prescribing or slow reduction or detoxification if appropriate, with regular reviews, and clinical decisions based on a careful and full assessment, including risk assessment, in collaboration with the full team and the patient. There is a paucity of research evaluating the most effective treatment for opiate detoxification in prisons. A study in which prison volunteers were randomly allocated to naltrexone implants or methadone before release showed reductions in both groups in the frequency of use of heroin and benzodiazepines, as well as criminality, six months after prison release. They also noted that, since the introduction of the schemes, there had been no attacks on staff or other prisoners with injecting equipment. A national programme of naloxone provision and training recently rolled out in Scotland for those deemed to be at risk of opioid overdose (and their family, friends, carers, and partners) includes prisoners who use opioid drugs on release from prison. It is hypothesised that this will reduce heroin overdose deaths in the first 12 weeks after release by 28 per cent. Recovery is about much more than avoiding harms, and while there is still debate about its definition,55 it is generally agreed to be about positive elements – positive development, achieving potential, contributing to the social milieu, and accessing and benefiting from the rights of that shared society. Recovery capital has been described as the ‘breadth and depth of internal and external resources that can be drawn upon to initiate and sustain recovery’ from substance use. They also have an important role in educating patients in the prison setting about reducing risks associated with drug use. Optimising the response of hospitals to drug problems requires the presence of consultation-liaison services to support staff in the management of withdrawal. This is particularly important for the prison population and for those newly released from prison. It is essential to recognise that these individuals have the same rights to accept or refuse treatment as the rest of the population. All doctors in clinical practice will encounter patients whose health is affected by use of psychoactive drugs. The basic competence required of all practitioners is the ability to recognise when drug use is contributing to health risks. This is achieved by history taking and examination, provision of appropriate advice, diagnosis of drug-related harm, and prescribing safely in a way that minimises the contribution of prescribed drugs to drug-related harm. The specific competencies required are discussed in more detail in a recent report from the Royal College of Psychiatrists and Royal College of General Practitioners, Delivering quality care for drug and alcohol users: the roles and competencies of doctors. Medical practitioners’ knowledge and experience of the biological, psychological and social factors predisposing to illicit drug use, and of the direct and secondary health harms of illicit drug use, have an important contribution to the development of prevention and treatment programmes. The following list summarises the data related to drug use, offences and treatment presented in various parts of this report. Over this time period, opiate and ecstasy use has remained relatively stable, amphetamine and hallucinogen use has declined slowly, and use of any cocaine has increased slightly (see Section 2. In a 1997 survey, over a quarter of the men who had used heroin reported first initiating use in prison (see Section 10. Hospital admission rates for drug-specific conditions for both male and female individuals have shown a strong positive association with deprivation (see Section 4. It is estimated that at least as much again is spent each year dealing with drug-related offences in the criminal justice system and prisons, while the wider social and economic costs of drug-related crime are estimated at around £16 billion a year in England and Wales (see Section 6. The level of use of opioid drugs has remained relatively unchanged over the last 15 years and most problematic drug use and drug-related deaths are associated with opiate use. Many patients who use illicit drugs come from the most marginalised sectors of society, and present with distinct and complex medical and social issues. By the time they present for treatment, they are likely to be socially marginalised or in prison. Their presenting complaints can be either directly or indirectly related to their drug use, but often mean that each patient requires a high level of care and attention. These patients are likely to be difficult to treat, as a result of feeling they have little to lose. It is essential that they are offered treatment in a non-judgemental way that includes aspects to support their social reintegration.

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For transverse loading on the spring generic zantac 300mg with visa gastritis diet virus, the relationship between F and z is not expected to be linear cheap zantac 300 mg free shipping gastritis colitis. Under load within the elastic limit buy zantac with visa chronic gastritis definition, the nanospring wire is twisted rather than stretched axially in the more usual testing geometry for a coiled spring. It is not subjected to the same effective loading in the way its nanowire analog would be in the three-point bend test. Values are tabulated for common bulk materials, but may in fact vary over a sample surface and are completely unknown when working with new materials, adding another dimension of uncertainty to the mechanics of nanosprings. The fundamental reasons for increased apparent elastic modulus in nanostructures remain unproved. There are multiple possible causes for these effects, including internal strain and specific atomic organization of the material. The mechanical properties of materials at nanoscale are determined not just by chemical compounds but also by the size and morphology of nanostructures. It is common to say that nanotechnology opens extra dimensions in the periodic table of elements. Phase contrast, pulsed-force, and other intermittent contact modes provide high spatial resolution of surfaces, highlighting inhomogeneities and relative surface property differences. Instrumentation and modeling have matured—and are con- stantly evolving—to where they offer a useful look into nanoscale mechanical per- formance. Although significant obstacles remain, the collection of recent advance- ments in nanomechanical measurements of material strength are laying a strong foundation to improve our understanding of basic material behavior such as beam bending and plastic deformation. Diameter-dependent elastic modulus supports the metastable-catalyst growth of carbon nanotubes. On the importance of boundary conditions on nanomechanical bending behavior and elastic modulus determination of silver nanowires. The technique is based on the relaxation properties of water protons, the most abun- dant nuclei in the human body. To overcome this deficiency of the technique, contrast agents are used to enhance the signal of the target by influencing the relaxation rates of local protons. Superparamagnetic agents, such as iron oxide, influence the sig- nal intensity by shortening T2 relaxation time predominantly; thereby, producing darker images as compared to surroundings and are consequently called negative *Contact at kumar070154@yahoo. Gd3+,Dy3+,Mn2+,Fe2+/3+,Cr3+) are known to mainly shorten T1 relaxation time of water protons, and consequently produce brighter images. Gadolinium (Gd3+) hydrolyzes under physiological conditions and precip- itates in the presence of inorganic phosphate, carbonate, and hydroxide. To prevent these toxic side effects, gadolinium chelates with high thermodynamic stability and kinetic inertia are required to keep gadolinium in solution and to increase the tolerance. In addition, low osmolality and viscosity along with rapid clearance are also needed. Linear and macrocyclic polyaminocarboxylate chelating agents are used to form ionic, nonionic, kinetically inert, and thermodynamically stable chelates. These agents were found very safe and efficacious in the preclinical and clinical settings. Fullerene-Based Nanostructures 333 polyaminocarboxylates form thermodynamically more stable and kinetically inert Gd3+ complexes than the chelates of linear polyaminocarboxylates; (ii) the relaxivity (mM−1 s−1) of these chelates is in the range of 3. These limitations are as follows: (i) High concentrations are needed to produce effective contrast owing to low relaxivity and diffusion effects experienced postinjection. Presumably, the pathology is a result of greater gadolinium release from the chelates because of slower clearance in these patients. The suscepti- bility of gadolinium chelates to dissociate in vivo and in vitro was recognized some time ago (5). A significant amount of work has been conducted in this area and is the subject of numerous review arti- cles (6–8). Fullerenes are created spontaneously when carbon is heated under low pressure in atmospheric conditions where there is little oxygen. Interestingly, researchers have found that they exist in nature and can be produced in small quantities simply by burning candles in a room with limited air. Similar conditions were used during antiquity to collect carbon soot to produce India ink, and fullerenes have been detected in the ink of Japanese manuscripts that are thousands of years old. Since the discovery of C60, other fullerenes, including C70,C72,C74,C76,C78, and C84, are also produced, some in smaller quantities. They are carbon crystals that are insoluble in water and in many organic solvents. Fullerene electrons do not completely saturate the available orbitals, so they have an intrinsic affinity for absorbing available electrons. Since their report and wide-scale availability, dissem- ination through the academic research community was rapid; since then, numerous applications have emerged. Derivatized water-soluble fullerenes are novel nano- materials, which are showing significant potential applications in biology and life sciences (10–14). It is important, at this point, to define fullerene and fullerene derivatives as nanoparticles. The icosahedral cage of C60 is approximately 1 nm in diameter, and other higher carbon fullerenes (C70,C72,C74,C76,C78, and C84) are only slightly larger. Thus, despite their molecular weight, fullerenes are similar in size to most small molecule therapeutics (unless these are aggregated)—an important property from the drug design and development perspective. Because of their spherical shape and tendency to aggregate, fullerenes are denoted commonly as nanoparticles. Some recent approaches have been focused with nanoparticulate platforms including gadolinium–silica, gadolinium–liposomes, perfluorocarbons, dendrimers, solid lipid, and gadolinium oxides. Fullerenes have hollow interiors inside, where other atoms and ions can be entrapped. Those materials that encapsulate metal atoms are called endohedral metallofullerens. In these cases, positive charge on the metal is balanced by the negative charge on the fullerene cage. For these applications, the most important property of the endohedral metallofullerene is highly stable encapsulation of metal ions. There is no covalent or coordinate bond formation, but rather the metal atoms are physically trapped inside the cage. The absence of any reactive site on the cage often makes the cage inert under physiological conditions. The metal inside the cage is not available by endogenously available ions and is not subject to any exchange or transmetallation, making it far more stable and inert than tradi- tional metal chelates. Recent work involves using derivatized gadofullerenes, Gd@C60, Gd@C82, and our own work by using Gd3N@C80. The Sc3N moiety is encapsulated in a highly symmetric, icosahedral C80 cage, which is stabilized as a result of charge transfer between nitride cluster and fullerene cage.

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Spermicidal agents 275 These include nonoxynol-9 300 mg zantac for sale gastritis diet , octoxinol and p-di-isobutylphenoxypoly(ethoxyethanol) purchase zantac 150mg online chronic gastritis frequently leads to. Spermicidal contraceptives are useful additional safeguards but do not give adequate contraceptive protection if used alone; they are suitable for use with barrier methods purchase zantac mastercard treating gastritis through diet. They have two components: a spermicide and a vehicle which itself may have some inhibiting effects on sperm activity. The systemic absorption of these drugs had previously been considered only from the standpoint of toxicity. However, in addition to local delivery, there has recently been considerable interest in the possibility of vaginal delivery for the systemic delivery of drugs, via the mucous membranes of the vagina. Current technologies in vaginal drug delivery are concerned with the systemic delivery of drugs such as estrogens, progesterones and prostaglandins. New technologies are exploring the systemic delivery of, for example, therapeutic peptides and proteins, via the vaginal route. This chapter reviews the structure and physiology of the vagina and the present and future utilization of the vagina for drug delivery. It is normally collapsed on itself and can hold between 2–3 g of fluid or gel without leakage to the outside. Microscopically, the vaginal wall consists of: • the epithelial layer, with underlying basement membrane; • the lamina propria (connective tissue); • the muscular layer; • the tunica adventitia (the vaginal fascia, which consists of loose connective tissue). The vaginal epithelium is composed of five different cell layers: • superficial (about 10 rows of cells): large polygonal cells with a high degree of proliferation, • transitional (about 10 rows of cells), • intermediate (about 10 rows of cells), • parabasal (2 rows of cells), • basal (single row of cells). An important aspect of the epithelium is an elaborate system of channels between the cells. These intercellular channels are capable of changing width as the hormone levels change during the menstrual cycle. The channels can accommodate rapid movement of leukocytes and large proteins such as IgG and albumin; they are an important pathway of watery secretion from the blood network to the tissue. The lamina propria contains a blood supply, a lymphatic drainage system, and a network of nerve fibers. It is through the blood vessels in the lamina propria that drugs can gain entry to the systemic circulation. Lymph drainage from the vagina takes place to the iliac sacral, gluteal, rectal, and inguinal lymphatic nodes. The changes are associated with aging (neonate, juvenile, adult and senescence), biphasic sexual cycling (follicular and luteal phases) and pregnancy. This proliferation of cells leads to an increase in epithelial thickness, as well as in the number of layers (Figure 11. A parallel increase in the number of intercellular junctions renders the epithelium more cohesive. The number of desmosomes increases approximately 10-fold from the early to late follicular phase. Luted phase During the luteal phase, desquamation (shedding) occurs on the superficial epithelial layer, extending as far as the intermediate cells. The vaginal surface loses its intact structure and the epithelium becomes loose and porous. This cyclic desquamation is preceded by loosening of intercellular grooves, as well as a pore- like widening of the intercellular channels. Rodents have an estrous cycle characterized by diestrous (Diest), proestrous, estrous (E) and metestrous phases (Figure 11. The cyclical changes in the epithelium of rodents are similar to the changes in human, i. The vaginal epithelium becomes extremely thin, cell boundaries in the surface are less distinct, the micro-ridges of the cells are dramatically reduced, and the vagina is often invaded with leukocytes. Naturally, this thinning of the epithelium leads to a substantial increase in the permeability of this tissue. Pregnancy During pregnancy the most marked change occurring in the vagina is increased vascularity and venous stasis, and the epithelial layer is greatly thickened. Following delivery, the vagina requires several weeks to reestablish its prepregnancy appearance. The vaginal fluid is composed of cervical fluid (the vagina receives approximately 2 g of mucus/day from the cervix) and also small amounts of the secretion from Bartholin’s glands in the vaginal wall. However, the bulk of fluid to the tissue, and the lumen of the tissue, comes via transudation of fluid (via the intercellular channels) from the very extensive vascular bed in the tissue. During the normal menstrual cycle, the amount of fluid increases at ovulation, by mixing with the uterine fluid, oviductal fluid, follicular fluid, and even peritoneal fluid. The vaginal secretions, which serve as a protective barrier for infections, contain a variety of antimicrobial substances including lysozyme, lactoferrin, fibronectin, polyamines such as spermine and secretory IgA. The fluids also contain carbohydrate from the epithelial glycogen, amino acids, aliphatic acids and proteins. The bioavailability of drugs administered via the vaginal route is dependent on both the effective dissolution of solid drug particles (if present) in the vaginal fluids prior to absorption and the degree of deactivation by enzymes present in the fluids. The physiological cyclical changes in the amount of vaginal fluids present in the vaginal cavity means that fluctuations in vaginal bioavailability can occur. This acidity plays a clinically important role in preventing the proliferation of pathogenic bacteria and there is a correlation between the pH of the vaginal secretions and the inhibition of chlamydial infections. Vaginal pH affects the degree of ionization of drugs, which can affect their absorption properties (see Section 1. Physiological changes in the pH of the vaginal fluids can also result in fluctuations in vaginal bioavailability. For example, using casein as a substrate, the proteolytic activity determined in a 10% homogenate of rat vaginal membrane was found to be less than that in the small intestine. The influence of the ovarian cycle on protease activity in the vagina has also been demonstrated. For example, the trypsin-like activity in rat vaginal smears was found to be maximal at proestrus. The activity of β-glucuronidase, acid phosphatase, alkaline phosphatase, and esterase all vary in the vaginal tissue of premenopausal and postmenopausal women. As described in general terms for the transepithelial absorption of drugs at any site (Section 1. In contrast, lipid-soluble drugs are usually absorbed transcellularly, by passive diffusion through the epithelium, down a concentration gradient according to Fick’s Law (Section 1. Drug diffusion rates correlate with their lipid/water diffusion coefficients and are inversely related to their molecular size (Section 1. However, these general observations do not take into account the cyclical changes in the vaginal epithelium, which exert profound effects on vaginal absorption, especially for hydrophilic compounds.

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When mitoxantrone is used in combination with other cytotoxic drugs proven 150mg zantac lymphocytic gastritis definition, these doses are often lower (Dunn & Goa 150 mg zantac free shipping antral gastritis diet plan, 1996; Royal Pharmaceutical Society of Great Britain cheap zantac 150 mg on line healthy liquid diet gastritis, 1999). In recent years, mitoxantrone has been used to a limited extent in the treatment of multiple sclerosis, typically at doses lower than those used in malignant disease and on a monthly schedule (Gonsettte, 1996; Millefiorini et al. Studies of Cancer in Humans The Working Group considered only studies in which mitoxantrone was given to patients who did not receive treatments with alkylating agents, with the exception of low doses of cyclophosphamide. A woman, 51 years old, with a primary breast tumour had received a combination of mitoxantrone, vincristine, 5-fluorouracil, cyclophosphamide and radiotherapy (chest and axillary); she developed acute promyelocytic leukaemia nine months later. The first case was that of a woman (aged 56 years) who received eight cycles of mitoxantrone (7 mg/m2), metho- trexate and mitomycin, local radiotherapy to the breast and axilla and tamoxifen. The second patient (aged 39 years) was also treated with eight cycles of mitoxantrone (7 mg/m2), methotrexate and mitomycin and in addition received radiotherapy to the breast. They had previously received radical mastectomy and either cyclophosphamide, metho- trexate and 5-fluorouracil or radiotherapy or both. Treatment with methotrexate, mito- xantrone and mitomycin was followed by tamoxifen, medroxyprogesterone acetate or medroxyprogesterone acetate and radiation therapy. Acute myeloid leukaemia (one case of acute monoblastic leukaemia, one of acute promyelocytic leukaemia and one of acute undifferentiated leukaemia) occurred 12–30 months after the start of treatment with the mitoxantrone-containing regimen. The patient had been treated with high doses of corticosteroids during exacerbation of the multiple sclerosis. Five years before the diagnosis of acute promyelocytic leukaemia, the patient had received an intravenous dose of mitoxantrone (10 mg/m2) once a month for five months (total dose, 87. The patient was reported to have no history of exposure to known leukaemogenic risk factors or a personal or family history of malignancy. Partridge and Lowdell (1999) reported the development of myelodysplastic syndrome in a 62-year-old woman treated for advanced breast cancer with five courses of mitoxantrone (7 mg/m2), methotrexate and mitomycin. In addition, she had received radiotherapy to the breast and axilla and tamoxifen. The planned doses for the intravenous regimen that included mitomycin (n = 30) were: mitoxantrone, 8 mg/m2 every three weeks (total dose, 64 mg); mito- mycin, 8 mg/m2 every six weeks (total dose, 32 mg) and methothrexate, 30 mg/m2 every three weeks (total dose, 240 mg). The planned doses for the intravenous regimen that did not include mitomycin (n = 29) were: mitoxantrone, 12 mg/m2 every three weeks (total dose, 96 mg) and methothrexate, 35 mg/m2 every three weeks (total dose, 280 mg). During follow-up for a median of 72 months, two cases of acute myeloid leukaemia (one of acute myelomonocytic leukaemia and one of acute myeloblastic leukaemia) and one case of myelodysplastic syndrome occurred. All three patients had received treatment without mitomycin in combination with tamoxifen (three cases), radiotherapy (one case) or other cytostatic drugs (one case). The interval between treatment and diagnosis was 17 and 18 months for the cases of acute myeloid leukaemia and 36 months for the case of myelodysplastic syndrome. The frequency of acute myeloid leukaemia and myelodysplastic syndrome was 3/59 (5%) in the two treatment groups combined and 3/29 in the group given treatment without mitomycin, who had received a higher dose of mitoxantrone and a slightly higher dose of methotrexate than the group treated with mitomycin. The dose of mitoxantrone associated with leukaemia was higher than that usually given in the treatment of advanced breast cancer. These were not considered further because the follow-up was rarely longer than one year and the patients would previously have been treated with leukaemogenic agents and/or radiation. Studies of Cancer in Experimental Animals No data were available to the Working Group. There are no published data on the bio- availability of orally administered mitoxantrone in humans, but a number of studies have reported the pharmacokinetics of mitoxantrone given as an intravenous infusion over 3–60 min at doses of 1–80 mg/m2. All showed an initial rapid phase representing distri- bution of the drug into blood cells, with a half-time of about 5 min (range, 2–16 min) and a long terminal half-time of about 30 h (range, 19–72 h) (Savaraj et al. Many early studies reported much shorter terminal half-times, but suitably sensitive assays may not have been used or adequate numbers of late samples collected. Tri-exponential elimination has been reported, the second distribution phase having a half-time of about 1 h (Alberts et al. The extent of the distribution into blood cells is illustrated by the observation that at the end of a 1-h infusion, the concentrations of mito- xantrone in leukocytes were 10 times higher than those in plasma (Sundman-Engberg et al. The typical peak plasma concentration after a 30–60-min infusion of 12 mg/m2 was about 500 ng/mL (Smyth et al. The rapid disappearance from plasma results in a total plasma clearance rate of about 500 mL/min, while the large volume of distribution of 500–4000 L/m2 indicates tissue sequestration of the drug (Savaraj et al. Studies of patients given mitoxantrone at doses up to 80 mg/m2 (standard dose, 12 mg/m2) suggest that the kinetics is linear up to this dose (Alberts et al. Studies of the urinary excretion of mitoxantrone concur that little of the admin- istered dose is cleared renally. In one study, urinary recovery of radiolabel after intravenous administration of [14C]mito- xantrone accounted for 6. The elimination half-time of mitoxantrone in two patients with impaired liver function was 63 h, whereas that in patients with normal liver function was 23 h (Smyth et al. Faecal recovery of radiolabel after a single 12 mg/m2 dose was 18% (range, 14–25%) over five days (Alberts et al. These results suggest that the liver is important in the elimination of mito- xantrone and that patients with impaired liver function or an abnormal fluid compart- ment may be at increased risk for toxic effects. The sequestration of mitoxantrone by body tissues results in retention of the drug for long periods. The characteristic blue–green colour of mitoxantrone has been observed on the surface of the peritoneum more than one month after intraperitoneal administration, and the concentrations in peritoneal tissue 6–22 weeks after intra- peritoneal dosing ranged from < 0. Mito- xantrone was readily detectable in post-mortem tissue samples from all 11 patients who had received mitoxantrone intravenously between 10 and 272 days before death. The highest concentrations were found in the thyroid, liver and heart and the lowest in brain tissue (Stewart et al. In one patient given [14C]mitoxantrone intra- venously, who died 35 days after the dose, as much as 15% of the administered dose could be accounted for in the liver, bone marrow, lungs, spleen, kidney and thyroid glands (Alberts et al. In one study, the fraction of unbound drug in plasma at the end of a 30-min infusion was only 3. Because of its limited urinary excretion, little information is available on the meta- bolism of mitoxantrone. Two inactive metabolites were identified in urine as the mono- and dicarboxylic acid derivatives resulting from oxidation of the terminal hydroxy groups of the side-chains (Figure 1) (Chiccarelli et al. The concentrations of mitoxantrone in urine were not altered by pre-incubation with a β-glucuronidase or sulfatase, suggesting that the drug is not excreted renally as either the glucuronide or sulfate conjugate (Smyth et al. This metabolite has been identified in the urine of patients given mitoxantrone (Blanz et al. After two further courses of 6 mg/m2 mitoxantrone, her breast milk contained 120 ng/mL mito- xantrone 3–4 h after dosing and 18 ng/mL by five days, and the concentration remained at this level for 28 days. This finding indicates that the drug is slowly released from a deep tissue compartment (Azuno et al. The drug was not developed for oral use, and in a review mito- xantrone was described as being poorly absorbed when administered orally [species not mentioned] (Batra et al. In rats, dogs and monkeys, the disappearance of intravenously administered [14C]- mitoxantrone from plasma was rapid, followed by a slow terminal elimination phase (James et al. Extensive tissue binding was indicated, with 50, 25 and 30% of the dose still retained 10 days after intravenous administration in rats, dogs and monkeys, respectively. In beagle dogs, tri- exponential elimination from plasma was reported, with a very rapid initial distribution phase with a half-time of 6.

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