Clin Pharmacokinet
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Randomized Controlled Trial
Population pharmacokinetics of daclizumab high-yield process in healthy volunteers: integrated analysis of intravenous and subcutaneous, single- and multiple-dose administration.
Daclizumab is a humanized monoclonal antibody that blocks the α-subunit of the interleukin-2 receptor with demonstrated benefits in the treatment of multiple sclerosis. The present work aimed to characterize the pharmacokinetics of daclizumab high-yield process (HYP) in healthy volunteers. ⋯ Daclizumab HYP is characterized by slow clearance, linear pharmacokinetics (at doses ≥100 mg), high subcutaneous bioavailability, and a half-life suitable for monthly administration.
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Observational Study
Midazolam pharmacokinetics in morbidly obese patients following semi-simultaneous oral and intravenous administration: a comparison with healthy volunteers.
While in vitro and animal studies have shown reduced cytochrome P450 (CYP) 3A activity due to obesity, clinical studies in (morbidly) obese patients are scarce. As CYP3A activity may influence both clearance and oral bioavailability in a distinct manner, in this study the pharmacokinetics of the CYP3A substrate midazolam were evaluated after semi-simultaneous oral and intravenous administration in morbidly obese patients, and compared with healthy volunteers. ⋯ In morbidly obese patients, systemic clearance of midazolam is unchanged, while oral bioavailability is increased. Given the large increase in volumes of distribution, dose adaptations for intravenous midazolam should be considered. Further research should elucidate the exact physiological changes at intestinal and hepatic level contributing to these findings.