Multiple-Dose Pharmacokinetics of Pentoxifylline and its Metabolites during Renal Insufficiency
| Autor: | Howard B Lassman, Karon S Simpson, Christopher M Paap, Marshall R Sack, Karen L Schaefer, Michael W. Horton |
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| Rok vydání: | 1996 |
| Předmět: |
Adult
Male medicine.medical_specialty Metabolite Population Cmax Urology Administration Oral Renal function 030226 pharmacology & pharmacy Pentoxifylline 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Oral administration Internal medicine medicine Humans Pharmacology (medical) Renal Insufficiency 030212 general & internal medicine education Aged education.field_of_study Cross-Over Studies Dose-Response Relationship Drug business.industry Middle Aged Crossover study Endocrinology chemistry Female business medicine.drug |
| Zdroj: | Annals of Pharmacotherapy. 30:724-729 |
| ISSN: | 1542-6270 1060-0280 |
| DOI: | 10.1177/106002809603000702 |
| Popis: | OBJECTIVE: To characterize pentoxifylline (PTF) and metabolite disposition after multiple oral doses given two and three times a day to patients with renal dysfunction. DESIGN: An open-label, randomized, crossover, parallel group design. SETTING: Community-based clinical research center. PATIENT POPULATION: Subjects with renal function stratified based on 24-hour urinary creatinine clearance (Clcr): group I = Clcr >80 mL/min (n = 9); group II = Clcr 30-80 mL/min (n = 6); and group III = Clcr METHODS: PTF 400 mg bid or tid was administered on days 1–7 and 400 mg bid or tid was given on days 14-20 with a 1-week washout. Timed blood samples were taken on days 1, 7, and 20. Blood samples were analyzed for PTF and its metabolites (M-I, M-IV, M-V) by gas-liquid chromatography. MAIN OUTCOME MEASURES: Maximum plasma concentration (Cmax), time to maximum concentration (tmax), average steady-state plasma concentration (Cssavg), and area under the plasma concentration-time curve at steady-state (AUCss) were determined by visual and model independent methods. ANOVA, paired t-test, and linear regression were used with significance level set at p < 0.05. RESULTS: The ratio of PTF AUCss (tid):AUCss (bid) and M-I AUCss (bid and tid) were not significantly different between the groups. Significant differences were found in M-IV and M-V Cmax, AUCss, Cssavg, and AUCss ratios (M-IV:PTF and M-V:PTF) between renal function groups (p < 0.05 for all). A change in dosage regimen from tid to bid resulted in significant changes in M-IV and M-V Cssavg for subjects with normal renal function and in those with moderate dysfunction, although not in subjects with severe renal dysfunction. CONCLUSIONS: Renal dysfunction did not cause significant accumulation of PTF or M-I after multiple bid and tid dosing; however, M-IV and M-V had significant accumulation in patients with renal impairment. Dosage reduction to 400 mg bid for patients with moderate renal impairment and 200-400 mg/d for severe renal impairment, as well as close clinical monitoring, seem prudent until the complex pharmacologic interactions of PTF and its metabolites can be further delineated. |
| Databáze: | OpenAIRE |
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