Abstract
This open-label study enrolled five subjects with biopsy-proven cirrhosis and moderate to severe hepatic impairment (Child-Pugh classification grade B or C) and five age- and gender-matched controls. All subjects received a single 40-mg oral dose of stavudine (d4T). Stavudine pharmacokinetics in subjects with hepatic impairment were similar to those in age- and gender-matched control subjects and were not substantially different from those previously observed in human immunodeficiency virus-infected patients. Based on these findings, stavudine use does not require modification of the dose or dosing interval for patients with liver disease.
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Selected References
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- Albers I., Hartmann H., Bircher J., Creutzfeldt W. Superiority of the Child-Pugh classification to quantitative liver function tests for assessing prognosis of liver cirrhosis. Scand J Gastroenterol. 1989 Apr;24(3):269–276. doi: 10.3109/00365528909093045. [DOI] [PubMed] [Google Scholar]
- Caregaro L., Menon F., Angeli P., Amodio P., Merkel C., Bortoluzzi A., Alberino F., Gatta A. Limitations of serum creatinine level and creatinine clearance as filtration markers in cirrhosis. Arch Intern Med. 1994 Jan 24;154(2):201–205. [PubMed] [Google Scholar]
- Cockcroft D. W., Gault M. H. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41. doi: 10.1159/000180580. [DOI] [PubMed] [Google Scholar]
- Dudley M. N., Graham K. K., Kaul S., Geletko S., Dunkle L., Browne M., Mayer K. Pharmacokinetics of stavudine in patients with AIDS or AIDS-related complex. J Infect Dis. 1992 Sep;166(3):480–485. doi: 10.1093/infdis/166.3.480. [DOI] [PubMed] [Google Scholar]
- Janiszewski J. S., Mulvana D. E., Kaul S., Dandekar K. A., Barbhaiya R. H. High-performance liquid chromatographic determination of 2',3'-didehydro-3'-deoxythymidine, a new anti-human immunodeficiency virus agent, in human plasma and urine. J Chromatogr. 1992 May 20;577(1):151–156. doi: 10.1016/0378-4347(92)80611-s. [DOI] [PubMed] [Google Scholar]
- Lea A. P., Faulds D. Stavudine: a review of its pharmacodynamic and pharmacokinetic properties and clinical potential in HIV infection. Drugs. 1996 May;51(5):846–864. doi: 10.2165/00003495-199651050-00009. [DOI] [PubMed] [Google Scholar]
- Locke C. S. An exact confidence interval from untransformed data for the ratio of two formulation means. J Pharmacokinet Biopharm. 1984 Dec;12(6):649–655. doi: 10.1007/BF01059558. [DOI] [PubMed] [Google Scholar]
- Murray H. W., Squires K. E., Weiss W., Sledz S., Sacks H. S., Hassett J., Cross A., Anderson R. E., Dunkle L. M. Stavudine in patients with AIDS and AIDS-related complex: AIDS clinical trials group 089. J Infect Dis. 1995 Mar;171 (Suppl 2):S123–S130. doi: 10.1093/infdis/171.supplement_2.s123. [DOI] [PubMed] [Google Scholar]
- Niederberger M., Schrier R. W. Pathogenesis of sodium and water retention in liver disease. Prog Liver Dis. 1992;10:329–347. [PubMed] [Google Scholar]
- Pugh R. N., Murray-Lyon I. M., Dawson J. L., Pietroni M. C., Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973 Aug;60(8):646–649. doi: 10.1002/bjs.1800600817. [DOI] [PubMed] [Google Scholar]
- Riegelman S., Collier P. The application of statistical moment theory to the evaluation of in vivo dissolution time and absorption time. J Pharmacokinet Biopharm. 1980 Oct;8(5):509–534. doi: 10.1007/BF01059549. [DOI] [PubMed] [Google Scholar]
- Skowron G. Biologic effects and safety of stavudine: overview of phase I and II clinical trials. J Infect Dis. 1995 Mar;171 (Suppl 2):S113–S117. doi: 10.1093/infdis/171.supplement_2.s113. [DOI] [PubMed] [Google Scholar]