Pharmacokinetics of saquinavir-SGC in HIV-infected pregnant women.
OBJECTIVE
To evaluate saquinavir (SQV) pharmacokinetics, tolerance, and safety in 10 HIV-infected pregnant women between 14-32 weeks gestation.


METHODS
This was a phase I, prospective, area-under-the-curve (AUC) targeted study. Antepartum treatment consisted of SQV 1200 mg tid, lamivudine 150 mg bid, and zidovudine 200 mg tid. The SQV targeted exposure was an 8-hour AUC (AUC(8)) of 3000 ng. h/mL; the study was to be halted if the first 4 participants did not achieve this AUC(8). Cord blood and plasma samples were collected in neonates at birth.


RESULTS
Four women completed the SQV pharmacokinetic assessments. Exposure in all 4 patients was below the target AUC(8). Median (range) AUC(8) and trough (C8H) were 1672 (738-2614) ng. h/mL and 60 (<15-332) ng/mL, respectively. Oral clearance (CL/F) was 9.3 (5.1-16.6) L/h/kg and C(max) was 599 (177-953) ng/mL. Cord and neonate plasma concentrations were mostly undetectable; 1 of 5 infants was HIV-infected at 24 weeks.


CONCLUSIONS
These data suggest highly variable SQV pharmacokinetics in pregnant women, and exposure at 1200 mg tid may not be adequate for longer term therapy; both the AUC(8) and C8H were considerably below average. Because ritonavir has been shown to significantly increase SQV concentrations, this combination should be further explored in this population.
Acosta
E P
EP
Division of Clinical Pharmacology, University of Alabama at Birmingham, 35294-0019, USA. EAcosta@uab.edu
Zorrilla
C
C
Van Dyke
R
R
Bardeguez
A
A
Smith
E
E
Hughes
M
M
Huang
S
S
Pitt
J
J
Watts
H
H
Mofenson
L
L
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D019540:Area Under Curve; D002214:Capsules; D004359:Drug Therapy, Combination; D005260:Female; D005780:Gelatin; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000635:transmission; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D019259:Lamivudine / Q000627:therapeutic use; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019258:Saquinavir / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D002214:Capsules; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D005780:Gelatin; D019258:Saquinavir