title: Pharmacokinetics, safety and efficacy of saquinavir/ ritonavir 1,000/100 mg twice daily as HIV type-1 therapy and transmission prophylaxis in pregnancy.
abstract: BACKGROUND
  A saquinavir/ritonavir-containing regimen is one option for the prevention of mother-to-child transmission of HIV during pregnancy. We evaluated the pharmacokinetics, efficacy and safety of saquinavir/ritonavir 1,000/100 mg twice daily plus nucleos(t)ide reverse transcriptase inhibitors in 13 women during late pregnancy and compared the results to those of 15 non-pregnant women.
  
  
  METHODS
  Protease inhibitor plasma concentration profiles were assessed at 12 h using a standardized therapeutic drug monitoring procedure and measured by LC-MS/MS. Minimum and maximum concentrations (C(min) and C(max)), area under the plasma concentration-time curve (AUC(0-12 h)), and total clearance (CL(total)) were compared between the groups and correlated to demographic, physiological and clinical cofactors. Antiviral and immunological efficacy and safety were investigated.
  
  
  RESULTS
  The geometric means (90% confidence interval [CI]) for saquinavir C(min), C(max) and AUC(0-2 h) of pregnant versus non-pregnant women were 572 (437-717) versus 765 (485-1,052, P = 0.064) ng/ml, 2,168 (1,594-2,807) versus 3,344 (2,429-4,350; P = 0.045) ng/ml and 15,512 (11,657-19,943) versus 24,027 (17,454-31,548, P = 0.029) ng x h/ml. The geometric means (90% CI) for ritonavir C(min), C(max) and AUC(0+12 h) were 190 (148-234) versus 310 (240-381, P = 0.011) ng/ml, 781 (580-999) versus 1,552 (1,127-2,007, P = 0.004) ng/ml and 5,576 (4,303-7,006) versus 10,528 (8,131-13,177, P = 0.003) ng x h/ml. Age, weight, saquinavir dose per weight and body mass index differed significantly; saquinavir C(min) and AUC(0-12 h) were correlated with ritonavir C(min) and saquinavir dose per weight. After a mean of 11 weeks treatment, 12 of 13 pregnant women had a viral load < 400 copies/ml, which was similar to the results of non-pregnant women.
  
  
  CONCLUSIONS
  Although saquinavir plasma concentrations were significantly lower in pregnant women compared with non-pregnant women, all pregnant women displayed a saquinavir AUC(0-12 h) > 10,000 ng x h/ml, 92.3% had a viral load < 400 copies/ml at birth. Saquinavir was well tolerated by the mothers and all newborn children were HIV type-1 negative at 18 months of age.
authors.affiliation: Pharmazentrum Frankfurt, Institute of Clinical Pharmacology, Johann Wolfgang Goethe University, Frankfurt, Germany. Hentig@em.uni-frankfurt.de
authors.forename: Nils
authors.initials: N
authors.lastname: von Hentig
authors.forename: Gabi
authors.initials: G
authors.lastname: Nisius
authors.forename: Tessa
authors.initials: T
authors.lastname: Lennemann
authors.forename: Pavel
authors.initials: P
authors.lastname: Khaykin
authors.forename: Christoph
authors.initials: C
authors.lastname: Stephan
authors.forename: Errol
authors.initials: E
authors.lastname: Babacan
authors.forename: Schlomo
authors.initials: S
authors.lastname: Staszewski
authors.forename: Michael
authors.initials: M
authors.lastname: Kurowski
authors.forename: Sebastian
authors.initials: S
authors.lastname: Harder
authors.forename: Annette
authors.initials: A
authors.lastname: Haberl
mesh_terms: D000328:Adult; D019540:Area Under Curve; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006207:Half-Life; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D011247:Pregnancy; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019258:Saquinavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D019258:Saquinavir; D019438:Ritonavir