Journal article
Pharmacokinetics of dirithromycin in patients with impaired hepatic function
Journal of antimicrobial chemotherapy, Vol.32(5), pp.741-750
11/1993
DOI: 10.1093/jac/32.5.741
PMID: 8125838
Abstract
Dirithromycin is a new macrolide antibiotic. A non-blinded, non-comparative study was performed in patients with mild, (Pugh and Childs Grade A) chronic, stable, impaired hepatic function (CSIHF) to determine the single- and multiple-dose pharmacokinetics and safety in such patients. Eight volunteers had disease affecting primarily the hepatic parenchyma, eight had primarily biliary system diseases and five healthy volunteers served as the control population. CSIHF patients and healthy volunteers all received a single dose of dirithromycin 500 mg po and 2 weeks later a 10-day course of dirithromycin 500 mg po once a day. Blood and urine samples were obtained with single dose administration and on days 1 and 10 of multiple-dose administration. The area under the serum concentration versus time curve (AUC) was higher with multiple-dose administration than with single-dose administration in all three treatment groups; however, the difference was not statistically significant between the treatment groups. With multiple-dose administration, peak serum concentrations (Cmax) were 0.69 ± 0.74, 0.34 ± 0.15, and 0.78 ± 0.25 mg/L and the AUC0–24 were 6.45 ± 6.27, 4.05 ± 1.59, and 6.60 ± 2.89 mg.h/L in normal, paren-chymal, and biliary volunteers, respectively. Cmax and AUC were consistently lower in subjects with parenchymal disease than those with biliary disease or normal volunteers but the reason for this is unclear. Statistically significant differences in clearance, due to lower non-renal and renal clearances in the biliary volunteers with single- or multiple-dose administration were found between the groups but these differences were not thought to be clinically or pharmacokinetically relevant for short-term antibiotic administration. With dirithromycin administered for 14 days or less, no dosage adjustment should be necessary in patients with mild hepatic insufficiency.
Details
- Title: Subtitle
- Pharmacokinetics of dirithromycin in patients with impaired hepatic function
- Creators
- D LaBreque - University of Iowa Hospitals and Clinics and Iowa City Department of Veterans Affairs Medical Center Iowa City, IAF Johlin - University of Iowa Hospitals and Clinics and Iowa City Department of Veterans Affairs Medical Center Iowa City, IAR Janda - University of Iowa Hospitals and Clinics and Iowa City Department of Veterans Affairs Medical Center Iowa City, IAT Shreves - University of Iowa Hospitals and Clinics and Iowa City Department of Veterans Affairs Medical Center Iowa City, IAD Gereats - University of Iowa Hospitals and Clinics and Iowa City Department of Veterans Affairs Medical Center Iowa City, IAK DeSante - Lilly Research Laboratories, Eli Lilly and Company Indianapolis, IN, USAB Cerimele - Lilly Research Laboratories, Eli Lilly and Company Indianapolis, IN, USAT Lanier - Lilly Research Laboratories, Eli Lilly and Company Indianapolis, IN, USAG Sides - Lilly Research Laboratories, Eli Lilly and Company Indianapolis, IN, USA
- Resource Type
- Journal article
- Publication Details
- Journal of antimicrobial chemotherapy, Vol.32(5), pp.741-750
- Publisher
- Oxford University Press
- DOI
- 10.1093/jac/32.5.741
- PMID
- 8125838
- ISSN
- 0305-7453
- eISSN
- 1460-2091
- Language
- English
- Date published
- 11/1993
- Academic Unit
- Gastroenterology and Hepatology; Internal Medicine
- Record Identifier
- 9984094585002771
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