Lopinavir tablet pharmacokinetics with an increased dose during pregnancy.
OBJECTIVE
Reduced lopinavir concentrations have been demonstrated with use of the capsule formulation during the third trimester of pregnancy. This study determined lopinavir exposure with an increased dose of the new tablet formulation during the third trimester.


METHODS
International Maternal Pediatric Adolescent AIDS Clinical Trials 1026s is a prospective nonblinded pharmacokinetic study in HIV-infected pregnant women, including a cohort receiving 2 lopinavir/ritonavir tablets (400 mg/100 mg) twice daily during the second trimester, 3 tablets (600 mg/150 mg) twice daily during the third trimester, and 2 tablets (400 mg/100 mg) twice daily post delivery through 2 weeks postpartum.


METHODS
Steady-state 12-hour pharmacokinetic profiles were performed during pregnancy and at 2 weeks postpartum. Lopinavir and ritonavir were measured by reverse-phase high-performance liquid chromatography (detection limit, 0.09 mcg/mL).


RESULTS
Thirty-three women were studied. Median lopinavir AUC for the second trimester (n = 11), third trimester (n = 33), and postpartum (n = 27) were 72, 96, and 133 mcg x hr/mL, respectively. Median minimum lopinavir concentrations were 3.4, 4.9, and 6.9 mcg/mL.


CONCLUSIONS
The higher lopinavir/ritonavir tablet dose (600 mg/150 mg) provided exposure during the third trimester similar to the average AUC (98 mcg x hr x mL(-1) in nonpregnant adults taking 400 mg/100 mg twice daily. The higher dose should be used during the second and third trimesters of pregnancy. Postpartum dosing can be reduced to standard dosing before 2 weeks postpartum.
Best
Brookie M
BM
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, CA, USA. brookie@ucsd.edu
Stek
Alice M
AM
Mirochnick
Mark
M
Hu
Chengcheng
C
Li
Hong
H
Burchett
Sandra K
SK
Rossi
Steven S
SS
Smith
Elizabeth
E
Read
Jennifer S
JS
Capparelli
Edmund V
EV
D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001835:Body Weight; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005006:Ethnicity; D005260:Female; D005865:Gestational Age; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir; D049590:Postpartum Period / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000821:virology*; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011744:Pyrimidinones / Q000493:pharmacokinetics* / Q000627:therapeutic use; D044469:Racial Groups; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D011744:Pyrimidinones; D061466:Lopinavir; D015215:Zidovudine