ArticleBritish journal of clinical pharmacology2007
Differential protein binding of indinavir and saquinavir in matched maternal and umbilical cord plasma.
Article in British journal of clinical pharmacology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Protecting the fetus against HIV infection: a systematic review of placental transfer of antiretrovirals.Clinical pharmacokinetics · 2014Pooled it
- (R)- and (S)-methadone and buprenorphine concentration ratios in maternal and umbilical cord plasma following chronic maintenance dosing in pregnancy.British journal of clinical pharmacology · 2010Trial
- Canine orosomucoid (alpha-1 acid glycoprotein) variants and their influence on drug plasma protein binding.Journal of veterinary pharmacology and therapeutics · 2021Article
- Placental transfer of maraviroc in an ex vivo human cotyledon perfusion model and influence of ABC transporter expression.Antimicrobial agents and chemotherapy · 2013Article
- Clinical therapeutics in pregnancy.Journal of biomedicine & biotechnology · 2011Article
- Binding of lopinavir to human alpha1-acid glycoprotein and serum albumin.Drug metabolism and disposition: the biological fate of chemicals · 2009Article
- Role of placental ATP-binding cassette (ABC) transporters in antiretroviral therapy during pregnancy.Journal of pharmaceutical sciences · 2009Review
- Functional role of p-glycoprotein and binding protein effect on the placental transfer of lopinavir/ritonavir in the ex vivo human perfusion model.Obstetrics and gynecology international · 2009Article
- Implications of gender and pregnancy for antiretroviral drug dosing.Current opinion in HIV and AIDS · 2008Article
- Concentration-effect and dose-response relations in clinical pharmacology.British journal of clinical pharmacology · 2007Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo determine whether lower umbilical cord than maternal binding of indinavir and saquinavir contributed to the low cord : maternal (C : M) total concentration ratios reported previously.
methodsIndinavir and saquinavir unbound fraction (fu) was determined using equilibrium dialysis. Buffer solutions of human serum albumin (HSA) (20.0, 30.0, 40.0 g l(-1)) and alpha(1)-acid glycoprotein (AAG) (0.20, 0.60, 2.00 g l(-1)) were spiked with indinavir (1.00 and 8.00 mg l(-1)) or saquinavir (0.15 and 1.50 mg l(-1)). Matched maternal and umbilical cord plasma was spiked with 1.00 mg l(-1) indinavir (n = 12) or 0.15 mg l(-1) saquinavir (n = 20). Spiked protein/plasma solutions were dialyzed against isotonic phosphate buffer, at 37 degrees C. At equilibrium, indinavir and saquinavir concentrations were quantified, and the f(u) determined.
resultsIndinavir and saquinavir demonstrated protein concentration-dependent binding in buffer solutions of HSA and AAG. Indinavir f(u) was significantly higher in umbilical cord (0.53 +/- 0.12) compared with maternal (0.36 +/- 0.11) plasma (95% CI of the difference -0.26, -0.097). Similarly, saquinavir fu was different between umbilical cord (0.0090 +/- 0.0046) and maternal plasma (0.0066 +/- 0.0039) (95% CI of the difference -0.0032, -0.0016). The transplacental AAG concentration gradient contributed significantly to the binding differential of both drugs.
conclusionsThe differential plasma binding of both drugs, which was largely the result of the transplacental AAG concentration gradient, would contribute to the low C : M total plasma concentration ratios observed previously. Unbound concentrations of indinavir and saquinavir are likely to be substantially lower in umbilical cord than maternal plasma.
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