scholarly journals No Need for Lopinavir Dose Adjustment during Pregnancy: a Population Pharmacokinetic and Exposure-Response Analysis in Pregnant and Nonpregnant HIV-Infected Subjects

2015 ◽  
Vol 60 (1) ◽  
pp. 400-408 ◽  
Author(s):  
Ahmed Hamed Salem ◽  
Aksana Kaefer Jones ◽  
Marilia Santini-Oliveira ◽  
Graham P. Taylor ◽  
Kristine B. Patterson ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Dose Adjustment ◽  
Population Pharmacokinetic Analysis ◽  
Tablet Formulation ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Virologic Suppression ◽  
Capsule Formulation ◽  
Mixed Effect ◽  
Hiv 1

ABSTRACTLopinavir-ritonavir is frequently prescribed to HIV-1-infected women during pregnancy. Decreased lopinavir exposure has been reported during pregnancy, but the clinical significance of this reduction is uncertain. This analysis aimed to evaluate the need for lopinavir dose adjustment during pregnancy. We conducted a population pharmacokinetic analysis of lopinavir and ritonavir concentrations collected from 84 pregnant and 595 nonpregnant treatment-naive and -experienced HIV-1-infected subjects enrolled in six clinical studies. Lopinavir-ritonavir doses in the studies ranged between 400/100 and 600/150 mg twice daily. In addition, linear mixed-effect analysis was used to compare the area under the concentration-time curve from 0 to 12 h (AUC0–12) and concentration prior to dosing (Cpredose) in pregnant women and nonpregnant subjects. The relationship between lopinavir exposure and virologic suppression in pregnant women and nonpregnant subjects was evaluated. Population pharmacokinetic analysis estimated 17% higher lopinavir clearance in pregnant women than in nonpregnant subjects. Lopinavir clearance values postpartum were 26.4% and 37.1% lower than in nonpregnant subjects and pregnant women, respectively. As the tablet formulation was estimated to be 20% more bioavailable than the capsule formulation, no statistically significant differences between lopinavir exposure in pregnant women receiving the tablet formulation and nonpregnant subjects receiving the capsule formulation were identified. In the range of lopinavir AUC0–12orCpredosevalues observed in the third trimester, there was no correlation between lopinavir exposure and viral load or proportion of subjects with virologic suppression. Similar efficacy was observed between pregnant women and nonpregnant subjects receiving lopinavir-ritonavir at 400/100 mg twice daily. The pharmacokinetic and pharmacodynamic results support the use of a lopinavir-ritonavir 400/100-mg twice-daily dose during pregnancy.

scholarly journals The influence of CYP2C8*3 on carbamazepine serum concentration in epileptic pediatric patients

2016 ◽  
Vol 19 (1) ◽  
pp. 21-28 ◽  
Author(s):  
DD Milovanovic ◽  
JR Milovanovic ◽  
M Radovanovic ◽  
I Radosavljevic ◽  
S Obradovic ◽  
...  
Keyword(s):  
Serum Concentration ◽  
High Performance ◽  
Dose Adjustment ◽  
Pediatric Patients ◽  
Plasma Concentrations ◽  
Clinical Importance ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Allele Specific

AbstractThe aim of the present study was to investigate the distribution of CYP2C8 variants *3 and *5, as well as their effect on carbamazepine pharmacokinetic properties, in 40 epileptic pediatric patients on carbamazepine treatment. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and allele-specific (AS)-PCR methods, and steady-state carbamazepine plasma concentrations were determined by high performance liquid chromatography (HPLC). The CYP2C8 *3 and *5 polymorphisms were found at frequencies of 17.5 and 0.0%, respectively. After dose adjustment, there was a difference in daily dose in CYP2C8*3 carriers compared to non carriers [mean ± standard deviation (SD): 14.19 ± 5.39 vs. 15.46 ± 4.35 mg/kg; p = 0.5]. Dose-normalized serum concentration of carbamazepine was higher in CYP2C8*3 (mean ± SD: 0.54 ± 0.18 vs. 0.43 ± 0.11 mg/mL, p = 0.04), and the observed correlation between weight-adjusted carbamazepine dose and carbamazepine concentration after dose adjustment was significant only in CYP2C8*3 non carriers (r = 0.52, p = 0.002). However, the population pharmacokinetic analysis failed to demonstrate any significant effect of CYP2C8 *3 polymorphism on carbamazepine clearance [CL L/h = 0.215 + 0.0696*SEX+ 0.000183*DD]. The results indicated that the CYP2C8*3 polymorphism might not be of clinical importance for epilepsy treatment in pediatric populations.

scholarly journals A Mechanism-Based Population Pharmacokinetic Analysis Assessing the Feasibility of Efavirenz Dose Reduction to 400 mg in Pregnant Women

2018 ◽  
Vol 57 (11) ◽  
pp. 1421-1433 ◽  
Author(s):  
Stein Schalkwijk ◽  
Rob ter Heine ◽  
Angela C. Colbers ◽  
Alwin D. R. Huitema ◽  
Paolo Denti ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Dose Reduction ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic

scholarly journals Population Pharmacokinetic Analysis of Voriconazole Plasma Concentration Data from Pediatric Studies

2008 ◽  
Vol 53 (3) ◽  
pp. 935-944 ◽  
Author(s):  
Mats O. Karlsson ◽  
Irja Lutsar ◽  
Peter A. Milligan
Keyword(s):  
Body Weight ◽  
Plasma Concentration ◽  
Patient Population ◽  
Pediatric Patients ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Time Data ◽  
Concentration Data ◽  
Mixed Effect

ABSTRACT Voriconazole is a potent triazole with broad-spectrum antifungal activity against clinically significant and emerging pathogens. The present population pharmacokinetic analysis evaluated voriconazole plasma concentration-time data from three studies of pediatric patients of 2 to <12 years of age, incorporating a range of single or multiple intravenous (i.v.) and/or oral (p.o.) doses. An appropriate pharmacokinetic model for this patient population was created using the nonlinear mixed-effect modeling approach. The final model described voriconazole elimination by a Michaelis-Menten process and distribution by a two-compartment model. It also incorporated a statistically significant (P < 0.001) influence of the CYP2C19 genotype and of the alanine aminotransferase level on clearance. The model was used in a number of deterministic simulations (based on various fixed, mg/kg of body weight, and individually adjusted doses) aimed at finding suitable i.v. and p.o. voriconazole dosing regimens for pediatric patients. As a result, 7 mg/kg twice a day (BID) i.v. or 200 mg BID p.o., irrespective of body weight, was recommended for this patient population. At these doses, the pediatric area-under-the-curve (AUC) distribution exhibited the least overall difference from the adult AUC distribution (at dose levels used in clinical practice). Loading doses or individual dosage adjustments according to baseline covariates are not considered necessary in administering voriconazole to children.

Pharmacogenetics-Based Population Pharmacokinetic Analysis of Efavirenz in HIV-1-Infected Individuals

2009 ◽  
Vol 85 (5) ◽  
pp. 485-494 ◽  
Author(s):  
M Arab-Alameddine ◽  
J Di Iulio ◽  
T Buclin ◽  
M Rotger ◽  
R Lubomirov ◽  
...  
Keyword(s):  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Hiv 1

Pharmacogenetics-based population pharmacokinetic analysis of etravirine in HIV-1 infected individuals

2013 ◽  
Vol 23 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Rubin Lubomirov ◽  
Mona Arab-Alameddine ◽  
Margalida Rotger ◽  
Aurélie Fayet-Mello ◽  
Raquel Martinez ◽  
...  
Keyword(s):  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Hiv 1

scholarly journals Population pharmacokinetic analysis of elvitegravir and cobicistat in HIV-1-infected individuals

2016 ◽  
Vol 71 (7) ◽  
pp. 1933-1942 ◽  
Author(s):  
Catalina Barceló ◽  
Frédéric Gaspar ◽  
Manel Aouri ◽  
Alice Panchaud ◽  
Margalida Rotger ◽  
...  
Keyword(s):  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Hiv 1
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