Assessment of pharmacokinetic proportionality of levofloxacin and cyclosporine over a 100-fold dose range in healthy human volunteers
| Autor: | Young-Ran Yoon, Jeonghyeon Park, Mi-sun Lim, Joomi Lee, Jeong Ju Seo, Hae Won Lee, Kyung Sang Yu, Sook Jin Seong |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Ofloxacin Cmax Administration Oral Biological Availability Levofloxacin Pharmacology Toxicology Washout period Young Adult Therapeutic index Dose proportionality Pharmacokinetics Tandem Mass Spectrometry medicine Humans Cross-Over Studies Dose-Response Relationship Drug business.industry Low dose General Medicine Middle Aged Anti-Bacterial Agents Area Under Curve Injections Intravenous Cyclosporine business Immunosuppressive Agents Half-Life medicine.drug |
| Zdroj: | Expert Opinion on Drug Metabolism & Toxicology. 8:399-405 |
| ISSN: | 1744-7607 1742-5255 |
| DOI: | 10.1517/17425255.2012.666237 |
| Popis: | Levofloxacin and cyclosporine show different pharmacokinetic properties, but are known to be dose proportional within the therapeutic range. The authors evaluated the pharmacokinetic proportionality of levofloxacin and cyclosporine over a 100-fold dose range in healthy human volunteers, by liquid chromatography-tandem mass spectrometry (LC-MS/MS).Two independent, randomized, crossover studies were performed. For levofloxacin, eight volunteers were randomly assigned in a 1:1 ratio to receive a low dose (7.5 mg) orally or intravenously, followed by a 1-week washout period and administration via the alternate route. After another 1-week washout period, a therapeutic dose (750 mg) was administered to all eight subjects. For cyclosporine, another eight volunteers received a low dose (2 mg) or a therapeutic dose (200 mg) orally with a 1-week washout period. Drug concentrations were determined by LC-MS/MS.For levofloxacin, the mean values for dose-normalized C(max) and AUC(last) with the two doses were as follows: therapeutic dose, 15.2 ± 4.6 ng/ml/mg and 103.6 ± 15.5 ng·h/ml/mg, respectively; low dose, 17.1 ± 6.5 ng/ml/mg and 72.6 ± 8.7 ng·h/ml/mg, respectively. For cyclosporine, the mean values for dose-normalized C(max) and AUC(last) were as follows: therapeutic dose, 4.9 ± 1.5 ng/ml/mg and 15.4 ± 4.9 ng·h/ml/mg, respectively; low dose, 1.6 ± 0.6 ng/ml/mg and 9.3 ± 7.3 ng·h/ml/mg, respectively.In this study levofloxacin, which is completely absorbed and primarily eliminated renally without modification, showed better pharmacokinetic proportionality than cyclosporine, which is poorly absorbed and extensively metabolized. |
| Databáze: | OpenAIRE |
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