PHARMACOKINETICS OF ZIDOVUDINE AND DIDEOXYINOSINE ALONE AND IN COMBINATION IN PATIENTS WITH THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME

Citation
M. Barry et al., PHARMACOKINETICS OF ZIDOVUDINE AND DIDEOXYINOSINE ALONE AND IN COMBINATION IN PATIENTS WITH THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME, British journal of clinical pharmacology, 37(5), 1994, pp. 421-426
Citations number
25
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
03065251
Volume
37
Issue
5
Year of publication
1994
Pages
421 - 426
Database
ISI
SICI code
0306-5251(1994)37:5<421:POZADA>2.0.ZU;2-F
Abstract
1 Zidovudine (ZDV) has proved unsuccessful in controlling disease prog ression over extended periods of time in patients with AIDS. Combinati on of ZDV with another reverse transcriptase inhibitor, dideoxyinosine (ddI) may improve the duration of effectiveness of antiretroviral the rapy. The aim of this study was to investigate the possibility of a ph armacokinetic drug interaction between ZDV and ddI. 2 The pharmacokine tics of ZDV and ddI were determined in eight patients with AIDS who we re randomised to receive ZDV 250 mg orally, ddI 250 mg orally or a com bination of ZDV 250 mg plus ddI 250 mg orally on 3 study days separate d by 1 week. 3 The administration of ZDV did not significantly alter d dI pharmacokinetics. The mean AUC was 6.8 +/- 2.0 s.d. and 7.6 +/- 2.5 s.d. mu mol 1(-1) h and oral clearance was 2766 +/- 686 and 2660 +/- 1297 ml min(-1) in the presence and absence of ZDV, respectively. 4 In the presence of ddI the elimination half-life of ZDV was increased si gnificantly by 18% from 1.1 +/- 0.3 to 1.3 +/- 0.3 h (P < 0.05) and th e mean AUC increased significantly by 35% from 4.8 +/- 1.5 to 6.5 +/- 1.5 mu mol 1(-1) h (P < 0.05). The clearance was decreased by 29% from 3518 +/- 1123 to 2505 +/- 575 ml min(-1), but this difference was not significant. The renal clearance of ZDV was not altered by ddI. 5 Adm inistration of ddI also resulted in a significant 22% increase in the AUC of GZDV, from 28.5 +/- 15.7 to 34.9 +/- 12.8 mu mol 1(-1) h (P < 0 .05). 6 Combination therapy with the nucleoside analogues ZDV and ddI may be the way forward in the treatment of advanced HIV disease, but t he pharmacokinetic drug interaction described here should be taken int o consideration.