Tinidazole Pharmacokinetics in Severe Renal Failure

Robson, Richard; Bailey, Ross R.; Sharman, John R.

doi:10.2165/00003088-198409010-00005

Cited by 7 publications

(6 citation statements)

References 5 publications

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“…It is unlikely that renal dysfunction will significantly alter the pharmacokinetics of the drug (Wood et al 1982). The pharmacokinetics of intravenous and oral tinidazole have been evaluated in patients with severe renal failure (Robson et al 1984). Following either route of administration, no differences were seen in elimination t,;, when compared with a control group of volunteers and no accumulation of the 2-hydroxymethyl metabolite was seen in either group.…”

mentioning

confidence: 99%

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Clinical Pharmacokinetics of Metronidazole and Other Nitroimidazole Anti-Infectives

Lau

Lam

Piscitelli

et al. 1992

Clinical Pharmacokinetics

182

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Metronidazole was first introduced for the treatment of trichomoniasis. Its therapeutic use has subsequently been expanded to include amoebiasis, giardiasis and, more recently, anaerobic infections. Most of the early pharmacokinetic studies employed nonspecific assays such as microbiological and chemical assays. These assays were not able to differentiate the parent drug from the metabolites or other interfering substances. Pharmacokinetic data obtained through the use of specific chromatographic techniques provide the basis for this review of recent pharmacokinetic findings concerning metronidazole and other nitroimidazole antibiotics. When given intravenously or orally at usual recommended doses, metronidazole attains concentrations well above the minimum inhibitory concentrations for most susceptible micro-organisms. The drug has an oral bioavailability approaching 100%. Rectal and vaginal administration results in a smaller amount of drug absorption and lower serum concentrations. Metronidazole has limited plasma protein binding but can attain very favourable tissue distribution, including into the central nervous system. The drug is extensively metabolised by the liver to form 2 primary oxidative metabolites: the hydroxy and acetic acid metabolites. The kidney is responsible for the elimination of only a small amount of the parent drug; however, normal excretion of the 2 metabolites is dependent on the integrity of kidney function. The metabolism of metronidazole was found to vary among patient groups. Preterm and term infants have lower total body clearance (CL) and prolonged elimination half-lives. However, children older than 4 years old were observed to have pharmacokinetic parameters similar to those in adults. Reduced CL was also observed in children who are malnourished. Elderly patients have reduced renal excretion of both the parent drug and hydroxy metabolite. Pharmacokinetic parameters in pregnant patients were not significantly different from those in nonpregnant women; however, the drug is distributed into breastmilk and the infant will be exposed to the drug through the nursing mother. Patients undergoing gastrointestinal surgery or having enteric diseases and those who are hospitalised or critically ill also have altered pharmacokinetics. Metabolism of the drug is reduced in patients with liver dysfunction, giving delayed production of metabolites. In contrast, renal failure has little effect on the elimination of the parent drug, but affects the excretion of the metabolites more significantly. Haemodialysis was found to remove a substantial amount of the metronidazole while the effect of peritoneal dialysis was more limited. Energy and protein deficient diets as well as occupational exposure to gasoline did not alter metronidazole pharmacokinetics. However, the effect of alcohol consumption on metronidazole CL requires further study.(ABSTRACT TRUNCATED AT 400 WORDS)

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confidence: 99%

“…Haemodialysis removed approximately 40% of the drug following a 6h session using a twin coil dialyser (Flouvat et al 1983). It has been suggested that a full or half dose of the drug be administered after dialysis (Flouvat et al 1983;Robson et al 1984).…”

mentioning

confidence: 99%

Clinical Pharmacokinetics of Metronidazole and Other Nitroimidazole Anti-Infectives

Lau

Lam

Piscitelli

et al. 1992

Clinical Pharmacokinetics

182

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“…The observed half-life of tinidazole in plasma was about 17 h, which was slighty longer than that reported by others; the published values have ranged from 12 to over 16 h [14][15][16][17][18]. Tinidazole was observed to persist slighty longer in blister fluid than in plasma, but the differences were statistically insignificant; the average half-lives were about 19 and 17 h, respectively.…”

Section: Resultsmentioning

confidence: 74%

“…5. Since not all samples of blister fluid were taken, the ratio of the con- [15][16][17]. As far as is known, there is no information about the penetration of the drug into cantharidin-induced skin blister fluid.…”

Section: Resultsmentioning

confidence: 99%

Penetration of tinidazole into skin blister fluid following its oral administration

Klimowicz

Nowak

Bielecka-Grzela

1992

Eur J Clin Pharmacol

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Plasma and skin blister fluid concentrations of tinidazole following a single oral dose of 2 g drug, and after multiple doses of 0.25 g every 12 h, were determined. Skin blisters were produced by direct application of 0.25% cantharidin ointment to the skin. The maximum concentration in plasma of about 36 mg.l-1 was observed after about 2 h, whereas in skin blister fluid the peak occurred after about 6 h and was 30 mg.l-1. The half-life in plasma was slightly shorter than in blister fluid at 17 and 19 h, respectively, but the difference was not significant. The penetration of tinidazole into cantharidin-induced skin blister fluid, defined according to Wise as the ratio of the AUCs in blister fluid and plasma was 1.00. During routine treatment with tinidazole (0.25 g every 12 h), the concentrations in plasma and blister fluid collected before and 3 h after the morning dose exceeded the minimal inhibitory concentrations for susceptible pathogens. The results provide a pharmacokinetic basis for the proven efficacy of tinidazole in the treatment of protozoal and anaerobic infections.

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“…Two studies investigating the plasma pharmacokinetics of DEC in patients with moderate and severe renal impairment could be identified (Table 3). (µg h/mL) [15] Diethylcarbamazine can be used for the treatment of different filarial diseases, such as lymphatic filariasis, loiasis, tropical pulmonary eosinophilia, and onchocerciasis. No tissue PK studies could be identified that met our requirements, except for one study that investigated the penetration of DEC into saliva (Table 2).…”

Section: Diethylcarbamazinementioning

confidence: 99%

Systemic and Target-Site Pharmacokinetics of Antiparasitic Agents

Jalali

Zeitlinger

2020

Clin Pharmacokinet

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About one-sixth of the world's population is affected by a neglected tropical disease as defined by the World Health Organization and Center for Disease Control. Parasitic diseases comprise most of the neglected tropical disease list and they are causing enormous amounts of disability, morbidity, mortality, and healthcare costs worldwide. The burden of disease of the top five parasitic diseases has been estimated to amount to a total 23 million disability-adjusted life-years. Despite the massive health and economic impact, most drugs currently used for the treatment of parasitic diseases have been developed decades ago and insufficient novel drugs are being developed. The current review provides a compilation of the systemic and target-site pharmacokinetics of established antiparasitic drugs. Knowledge of the pharmacokinetic profile of drugs allows for the examination and possibly optimization of existing dosing schemes. Many symptoms of parasitic diseases are caused by parasites residing in different host tissues. Penetration of the antiparasitic drug into these tissues, the target site of infection, is a prerequisite for a successful treatment of the disease. Therefore, for the examination and improvement of established dosing regimens, not only the plasma but also the tissue pharmacokinetics of the drug have to be considered. For the current paper, almost 7000 scientific articles were identified and screened from which 429 were reviewed in detail and 100 were included in this paper. Systemic pharmacokinetics are available for most antiparasitic drugs but in many cases, not for all the relevant patient populations and only for single-or multiple-dose administration. Systemic pharmacokinetic data in patients with organ impairment and target-site pharmacokinetic data for relevant tissues and body fluids are mostly lacking. To improve the treatment of patients with parasitic diseases, research in these areas is urgently needed.

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Tinidazole Pharmacokinetics in Severe Renal Failure

Cited by 7 publications

References 5 publications

Clinical Pharmacokinetics of Metronidazole and Other Nitroimidazole Anti-Infectives

Clinical Pharmacokinetics of Metronidazole and Other Nitroimidazole Anti-Infectives

Penetration of tinidazole into skin blister fluid following its oral administration

Systemic and Target-Site Pharmacokinetics of Antiparasitic Agents

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