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Trough Plasma Concentration (trough + plasma_concentration)

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Medical Sciences100%

Selected Abstracts

Cytochrome P450 2D6 genotype does not predict SSRI (fluoxetine or paroxetine) induced hyponatraemia

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2002
Catherine A. M. Stedman
Abstract Aims The aims of this study were to determine if patients with SSRI-related hyponatraemia were (1) genetically poor metabolizers of CYP2D6, and/or (2) had excessive plasma concentrations of the SSRI antidepressant. Methods Plasma DNA from 20 people with hyponatraemia attributable to fluoxetine or paroxetine was analysed for the CYP2D6 alleles *1,*16. Trough plasma concentrations of fluoxetine and norfluoxetine, or paroxetine were assayed in nine people who remained on the antidepressant. Results Genotype results were compared with those published in a large population study. The poor metabolizer PM/PM genotype was present in one subject only, or 5% of the study population, compared with 7.2% of a general population. The 95% Cl of this result was 0,21%, suggesting that it is most unlikely that hyponatremia is related to the PM/PM genotype. The intermediate IM/PM genotype was present in 5% compared with 19.7% of a general population. All differences were not statistically significant. Antidepressant concentrations of fluoxetine (n,=,5, all EM) and paroxetine (n,=,1,IM/PM and n,=,3,EM) were all within the lower half of the reference range. Conclusions These results do not support the hypothesis that SSRI-related hyponatraemia is linked to genetically poor metabolizers, or excessive drug concentrations. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Low initial trough plasma concentrations of lopinavir are associated with an impairment of virological response in an unselected cohort of HIV-1-infected patients

HIV MEDICINE, Issue 3 2006
MI Wateba
Objectives The relationship between lopinavir trough plasma concentration at baseline and virological efficacy 3 months after the beginning of the therapy was investigated in an unselected cohort of HIV-1-infected patients Methods According to initial trough lopinavir plasma level, patients were classified into three groups: the subtherapeutic group (<3 mg/L, n=18), the therapeutic group (between 3 and 8 mg/L, n=50) and the toxic group (>8 mg/L, n=16). The virological response after 3 months of lopinavir treatment, defined as a viral load <200 HIV-1 RNA copies/mL, was compared amongst these groups. Results The virological response was significantly different (P<0.05) between the subtherapeutic group (22.% of patients with viral load<200 copies/mL) and the other groups (56.0% of patients with a viral load<200 copies/mL in the therapeutic group and 56.2% in the toxic group). Conclusions A lower virological efficacy should be expected for experienced or naive patients with plasma trough lopinavir concentrations<3 mg/L at the beginning of treatment. [source]

Pharmacokinetics and tolerability of modafinil tablets in Chinese subjects

JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2008
P. Xu PhD
Summary Objective:, To investigate the pharmacokinetics and tolerability of modafinil in Chinese subjects. Methods:, Twelve healthy volunteers were given an escalating single dose of modafinil (100, 200 and 400 mg) in a three-period study (study 1). Another 12 volunteers received 100 mg twice daily for 7 days in multiple-dose study (study 2). Blood samples were taken from 0 to 60 h for study 1. And samples for study 2 were collected before administration on three consecutive morning and then from 0 to 60 h after the last dose. Pharmacokinetic parameters were calculated and compared with results from published data. Results:, In study 1, Cmax and area under the concentration,time curve of modafinil and modafinil acid were increased proportionally with dose levels; t1/2 was independent on the dose levels. In study 2, the steady state was reached on day 4, and mean trough plasma concentration of modafinil was 1·36 ± 0·34 ,g/mL. Apparent plasma clearance and apparent volume of distribution were lower in 100 mg twice-daily group than those in 100 mg single group. The adverse events were mild and moderate in study 1 and 2. Conclusions:, In this pharmacokinetic study, modafinil was safe and well tolerated by young healthy Chinese subjects. The major pharmacokinetic parameters of modafinil in Chinese subjects are similar to those reported in Caucasians although the half-life seems to be longer in the former than in the latter. This apparent difference requires investigation. [source]

Low initial trough plasma concentrations of lopinavir are associated with an impairment of virological response in an unselected cohort of HIV-1-infected patients

HIV MEDICINE, Issue 3 2006
MI Wateba
Objectives The relationship between lopinavir trough plasma concentration at baseline and virological efficacy 3 months after the beginning of the therapy was investigated in an unselected cohort of HIV-1-infected patients Methods According to initial trough lopinavir plasma level, patients were classified into three groups: the subtherapeutic group (<3 mg/L, n=18), the therapeutic group (between 3 and 8 mg/L, n=50) and the toxic group (>8 mg/L, n=16). The virological response after 3 months of lopinavir treatment, defined as a viral load <200 HIV-1 RNA copies/mL, was compared amongst these groups. Results The virological response was significantly different (P<0.05) between the subtherapeutic group (22.% of patients with viral load<200 copies/mL) and the other groups (56.0% of patients with a viral load<200 copies/mL in the therapeutic group and 56.2% in the toxic group). Conclusions A lower virological efficacy should be expected for experienced or naive patients with plasma trough lopinavir concentrations<3 mg/L at the beginning of treatment. [source]