Relationship between body weight, body surface area and serum zidovudine pharmacokinetic parameters in adult, male HIV-infected patients.
OBJECTIVE
To determine whether there is a simple relationship between body weight or body surface area (BSA) and serum zidovudine pharmacokinetic parameters in patients receiving oral zidovudine.


METHODS
Single-dose, pharmacokinetic study.


METHODS
Fifty-three asymptomatic and symptomatic HIV-infected men (CD4+ cell count < 500 x 10(6)/l) participated in the study. Results of renal function and haematology tests were within normal limits and all hepatic function tests were up to three times the upper limit of normal. Patients received 200 mg oral zidovudine and serial blood samples were collected for 4 h (18 patients) or 8 h (35 patients). Serum zidovudine concentrations were measured by high-performance liquid chromatography (12 patients) or radioimmunoassay (41 patients). Pharmacokinetic parameters were calculated by non-compartmental methods. The relationships between body weight or BSA and maximum serum concentration (Cmax), area under the concentration-time curve (AUC), apparent serum clearance (CL/F), and apparent terminal volume of distribution (Vz/F) were determined by simple least-squares linear regression.


RESULTS
There were no significant relationships between either body weight or BSA and Cmax, AUC, Vz/F (corrected for weight), and clearance (P > 0.07; R2 < 0.06 for all comparisons). A significant positive association between Vz/F, uncorrected for weight, and either weight (P = 0.011; R2 = 0.121) or BSA (P = 0.022; R2 = 0.098) was observed. The interindividual coefficients of variation of CL/F and Vz/F values were only marginally reduced when the parameters were corrected for weight (31.3 versus 30.8% and 28.0 versus 26.0% respectively).


CONCLUSIONS
There is little or no linear association between either body weight or BSA and observed serum zidovudine concentrations following administration of 200 mg zidovudine in adult male patients who are within 20% of their ideal weight.
Sahai
J
J
University of Ottawa AIDS Research Group, Ottawa General Hospital, Ontario, Canada.
Gallicano
K
K
Ormsby
E
E
Garber
G
G
Cameron
D W
DW
D000328:Adult; D001830:Body Surface Area; D001835:Body Weight; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015215:Zidovudine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D015215:Zidovudine