Pharmacokinetic Properties of Anti-Influenza Neuraminidase Inhibitors.

Neuraminidase inhibitors are the mainstay of anti-influenza treatment. Oseltamivir is the most widely used drug but is currently available only as an oral formulation. Resistance spreads rapidly in seasonal H1N1 influenza A viruses, which were universally resistant in 2008, because of the H275Y mutation in the neuraminidase (NA) gene. Oseltamivir is a prodrug for the active carboxylate metabolite. Ex vivo conversion in blood samples may have confounded early pharmacokinetic studies. Oseltamivir shows dose linear kinetics, and oseltamivir carboxylate has an elimination half-life (t(andfrac12;β)) after oral administration in healthy individuals of approximately 7.7 hours. Oseltamivir carboxylate is eliminated primarily by tubular secretion, and both clearance and tissue distribution are reduced by probenecid. The H275Y mutation in NA confers high-level oseltamivir resistance and intermediate peramivir resistance but does not alter zanamivir susceptibility. Zanamivir is available as a powder for inhalation, and a parenteral form is under development. Zanamivir distributes in an apparent volume of distribution approximating that of extracellular water and is rapidly eliminated (t(andfrac12;β) of approximately 3.0 hours). Peramivir is slowly eliminated (t(andfrac12;β) of 7.7-20.8 hours) and is prescribed as either a once-daily injection or as a single infusion. Laninamivir is a recently developed slowly eliminated compound for administration by inhalation

Population pharmacokinetics of oseltamivir and oseltamivir carboxylate in obese and Non-obese volunteers.

The aims of this study were to compare the pharmacokinetics of oseltamivir and oseltamivir carboxylate in obese and non-obese individuals and to determine the effect of obesity on the pharmacokinetic properties of oseltamivir and the active antiviral metabolite oseltamivir carboxylate.The population pharmacokinetic properties of oseltamivir and oseltamivir carboxylate were evaluated in 12 obese (body mass index; BMI ≥30 kg/m(2) ) and 12 non-obese (BMI <30 kg/m(2) ) Thai adult volunteers receiving a standard dose of 75 mg and a double dose of 150 mg in a randomised sequence. Concentration-time data were collected and analysed with nonlinear mixed-effects modelling.The pharmacokinetics of oseltamivir and its active metabolite, oseltamivir carboxylate, were described simultaneously by first-order absorption, with a one-compartment disposition model for oseltamivir followed by a metabolism compartment and one-compartment disposition of oseltamivir carboxylate. Creatinine clearance was a significant predictor of oseltamivir carboxylate clearance (3.84% increase for each 10 mL/min increase of creatinine clearance, 95% confidence interval [95% CI] of 0.178 to 8.02%). Obese individuals had an approximately 25% (95% CI of 24% to 28%) higher oseltamivir clearance, 20% higher oseltamivir volume of distribution (95% CI of 19% to 23%) and 10% higher oseltamivir carboxylate clearance (95% CI of 9% to 11%) compared to non-obese individuals. However, these altered pharmacokinetic properties were small and did not change the overall exposure to oseltamivir carboxylate.This confirmed that dose adjustment of oseltamivir in obese individuals was not necessary on a pharmacokinetic basis

Enantiospecific pharmacokinetics and drug-drug interactions of primaquine and blood-stage antimalarial drugs

Objectives Characterization of the pharmacokinetic properties of the enantiomers of primaquine and carboxyprimaquine following administration of racemic primaquine given alone and in combination with commonly used antimalarial drugs. Methods Enantiomeric pharmacokinetics were evaluated in 49 healthy adult volunteers enrolled in three randomized cross-over studies in which a single dose of primaquine was given alone and then, after a suitable washout period, in combination with chloroquine, dihydroartemisinin/piperaquine or pyronaridine/artesunate. Non-linear mixed-effects modelling was used to characterize pharmacokinetics and assess the impact of drug–drug interactions. Results The volume of distribution of racemic primaquine was decreased by a median (95% CI) of 22.0% (2.24%–39.9%), 24.0% (15.0%–31.5%) and 25.7% (20.3%–31.1%) when co-administered with chloroquine, dihydroartemisinin/piperaquine and pyronaridine/artesunate, respectively. The oral clearance of primaquine was decreased by a median of 19.1% (14.5%–22.8%) when co-administered with pyronaridine/artesunate. These interactions were enantiospecific with a relatively higher effect on (+)-S-primaquine than on (−)-R-primaquine. No drug–drug interaction effects were seen on the pharmacokinetics of either carboxyprimaquine enantiomer. Conclusions Population pharmacokinetic models characterizing the enantiospecific properties of primaquine were developed successfully. Exposure to primaquine, particularly to the (+)-S-primaquine but not the carboxy metabolites, increased by up to 30% when co-administered with commonly used antimalarial drugs. A better mechanistic understanding of primaquine metabolism is required for assessment of its efficacy and haematological toxicity in humans

Enantiospecific pharmacokinetics and drug-drug interactions of primaquine and blood-stage antimalarial drugs

Objectives Characterization of the pharmacokinetic properties of the enantiomers of primaquine and carboxyprimaquine following administration of racemic primaquine given alone and in combination with commonly used antimalarial drugs. Methods Enantiomeric pharmacokinetics were evaluated in 49 healthy adult volunteers enrolled in three randomized cross-over studies in which a single dose of primaquine was given alone and then, after a suitable washout period, in combination with chloroquine, dihydroartemisinin/piperaquine or pyronaridine/artesunate. Non-linear mixed-effects modelling was used to characterize pharmacokinetics and assess the impact of drug–drug interactions. Results The volume of distribution of racemic primaquine was decreased by a median (95% CI) of 22.0% (2.24%–39.9%), 24.0% (15.0%–31.5%) and 25.7% (20.3%–31.1%) when co-administered with chloroquine, dihydroartemisinin/piperaquine and pyronaridine/artesunate, respectively. The oral clearance of primaquine was decreased by a median of 19.1% (14.5%–22.8%) when co-administered with pyronaridine/artesunate. These interactions were enantiospecific with a relatively higher effect on (+)-S-primaquine than on (−)-R-primaquine. No drug–drug interaction effects were seen on the pharmacokinetics of either carboxyprimaquine enantiomer. Conclusions Population pharmacokinetic models characterizing the enantiospecific properties of primaquine were developed successfully. Exposure to primaquine, particularly to the (+)-S-primaquine but not the carboxy metabolites, increased by up to 30% when co-administered with commonly used antimalarial drugs. A better mechanistic understanding of primaquine metabolism is required for assessment of its efficacy and haematological toxicity in humans

Political Participation Instruction for Monk and Novice Students in Thailand

This research aimed (1) to study the political participation of the monk and novice students in MCUKK as the guideline to develop the political participation instruction for MCUKK students, (2) to suggest the ways to promote the political participation instruction of the monk and novice students. The population of the research was the bachelor degree students: monks and novices (n = 266) of MCUKK. The key informants (15) including 1 educational administrator, 2 directors of Political Science Programs (Bachelor and Master), and 2 lecturers, 10 students selected by Purposive Sampling. This study was conducted by means of the mixed research methodology: quantitative research and qualitative research. The tools used in this research were the five-rating scale questionnaire and an in-depth interview. The research findings indicated that (1) the political participation of the students in four studied aspects were statistically rated the moderate level; (2) the university lecturers should pay attention to educating the legal rights and importance of political participation in terms of voting, political news, political campaign and political rally for the students. The finding suggested that teaching political participation should be managed properly, although there is the law that prohibits monks or novices to get involved in politics