title: Pharmacokinetic study of saquinavir 500 mg plus ritonavir (1000/100 mg twice a day) in HIV-positive pregnant women.
abstract: Antiretroviral therapy during pregnancy is critical to preventing human immunodeficiency virus vertical transmission. Physiological changes during pregnancy can alter drug kinetics. The aim of this study was to assess the pharmacokinetics (PK) of saquinavir (SQV) boosted with ritonavir during pregnancy and postpartum. Fourteen human immunodeficiency virus-positive pregnant women started SQV 500 mg new tablet formulation plus ritonavir at a dose of 1000/100 mg twice a day + 2 nucleoside retrotranscriptase inhibitors during pregnancy. At weeks 24 and 34 of pregnancy and 6 weeks postpartum, a 12-hour PK study was conducted. PK parameters were calculated using Win Nolin software version 4.1. At week 24, the geometric mean values for SQV area under the plasma concentration-time curve from 0-12 hours (AUC₀₋₁₂), the maximum observed plasma concentration (C(max)), trough plasma concentration (C(min)), and the elimination half-life (t(1/2)) were 24.80 mg·h⁻¹·mL⁻¹, 4.66 mg/mL, 0.93 mg/mL, and 4.31 hours, respectively. At week 34, AUC₀₋₁₂, C(max), C(min), and t(1/2) were 12.71 mg·h⁻¹·mL⁻¹, 3.23 mg/mL, 0.26 mg/mL, and 4.06 hours, respectively. Finally, at 6 weeks postpartum, mean values for SQV AUC₀₋₁₂, C(max), C(min), and t(1/2) were 28.94 mg·h⁻¹·mL⁻¹, 3.92 mg/mL, 0.86 mg/mL, and 3.60 hours, respectively. Although PK parameters in week 24 and postpartum were very similar, those for week 34 showed an important reduction: -71.20%, -30.61%, -48.73%, and -5.81% in C(min), C(max), AUC₀₋₁₂, and t(1/2), respectively, compared with week 24, but no statistically significant differences were shown between patients. No vertical transmissions were reported. Therapeutic drug monitoring of SQV during pregnancy should be considered, mainly during the third trimester, to ensure adequate drug exposure throughout the entire pregnancy.
authors: Infectious Diseases Service, IDIBAPS, Hospital Clínic, Barcelona, Spain. rebollar@clinic.ub.es
authors: Maria
authors: M
authors: Martinez-Rebollar
authors: Montserrat
authors: M
authors: Lonca
authors: Iñaki
authors: I
authors: Perez
authors: Dolors
authors: D
authors: Soy
authors: Mercè
authors: M
authors: Brunet
authors: Rosa
authors: R
authors: Martin
authors: Oriol
authors: O
authors: Coll
authors: Sandra
authors: S
authors: Hernandez
authors: Montserrat
authors: M
authors: Laguno
authors: Ana
authors: A
authors: Milinkovic
authors: Maria
authors: M
authors: Larrousse
authors: Marta
authors: M
authors: Calvo
authors: Jose L
authors: JL
authors: Blanco
authors: Esteban
authors: E
authors: Martínez
authors: Jose M
authors: JM
authors: Gatell
authors: Josep
authors: J
authors: Mallolas
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006679:HIV Seropositivity / Q000097:blood* / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D050177:Overweight / Q000150:complications; D010865:Pilot Projects; D049590:Postpartum Period; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011446:Prospective Studies; D019438:Ritonavir / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019258:Saquinavir / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D017320:HIV Protease Inhibitors; D019258:Saquinavir; D019438:Ritonavir