Pharmacokinetic variability of zidovudine in HIV-infected individuals: subgroup analysis and drug interactions.
OBJECTIVE
To investigate determinants of inter- and intraindividual variability of zidovudine (ZDV) pharmacokinetics in HIV-infected patients.


METHODS
A prospective study in a general 525-bed hospital with special funding for treatment and research of HIV-infected patients.


METHODS
Serial blood samples were collected from 68 HIV-infected individuals providing a total of 95 pharmacokinetic curves. ZDV was measured with high-performance liquid chromatography and radioimmunoassay. Pharmacokinetic parameters were calculated by non-compartmental analysis. Patient characteristics were investigated by multivariate analysis for an influence on ZDV pharmacokinetics.


RESULTS
Apparent ZDV clearance was significantly lower in patients with a lower body weight, in women, and in patients with a more advanced stage of HIV disease. Co-administration of methadone with ZDV resulted in higher plasma concentrations of ZDV, while rifampin and ganciclovir increased apparent ZDV clearance. Age, the duration of ZDV use, CD4+ cell count, creatinine clearance, elevated serum liver enzyme levels, and the use of 11 other co-administered medications were not independently related to apparent ZDV clearance.


CONCLUSIONS
The pharmacokinetic profile of ZDV in several subpopulations has been evaluated, as well as the observation of possible drug-drug interactions between ZDV and 14 different drugs or groups of drugs. These data suggest that patient-individualized antiretroviral therapy may be appropriate once pharmacokinetic-pharmacodynamic relationships have been established.
Burger
D M
DM
Department of Pharmacy, Slotervaart Hospital, Amsterdam, The Netherlands.
Meenhorst
P L
PL
ten Napel
C H
CH
Mulder
J W
JW
Neef
C
C
Koks
C H
CH
Bult
A
A
Beijnen
J H
JH
D000328:Adult; D000367:Age Factors; D000368:Aged; D001835:Body Weight; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008099:Liver / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012727:Sex Characteristics; D015215:Zidovudine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D015215:Zidovudine