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
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.