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sex differences, pharmacokinetics

Johannes Matthaei, Mladen V Tzvetkov, Valerie Gal, Cordula Sachse-Seeboth, Daniel Sehrt, Jakob B Hjelmborg, Ute Hofmann, Matthias Schwab, Reinhold Kerb, Jürgen Brockmöller
BACKGROUND: Efflux transporters like MDR1 and MRP2 may modulate the pharmacokinetics of about 50 % of all drugs. It is currently unknown how much of the variation in the activities of important drug membrane transporters like MDR1 or MRP2 is determined by genetic or by environmental factors. In this study we assessed the heritability of the pharmacokinetics of talinolol as a putative probe drug for MDR1 and possibly other membrane transporters. METHODS: Talinolol pharmacokinetics were investigated in a repeated dose study in 42 monozygotic and 13 same-sex dizygotic twin pairs...
November 8, 2016: Genome Medicine
Andrea Salzano, Pablo Demelo-Rodriguez, Alberto Maria Marra, Marco Proietti
BACKGROUND: The biological differences among male and female, based on distinctive expression of sex chromosomes, on varied gene-expression and on peculiar sexual hormones, lead to important differences in physiology and pathophysiology. OBJECTIVE: The aim of this work was to briefly review the relationships among gender-related differences and clinical implications in antithrombotic therapy, that could be related to sex-differences in platelet biology and coagulation reactions...
October 29, 2016: Current Medicinal Chemistry
D D Milovanovic, J R Milovanovic, M Radovanovic, I Radosavljevic, S Obradovic, S Jankovic, D Milovanovic, N Djordjevic
The 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...
July 1, 2016: Balkan Journal of Medical Genetics: BJMG
Joel E Gallant, Graeme Moyle, Juan Berenguer, Peter Shalit, Huyen Cao, Ya-Pei Liu, Joel Myers, Lisa Rosenblatt, Lingfeng Yang, Javier Szwarcberg
OBJECTIVES: Cobicistat (COBI) enhances atazanavir (ATV) pharmacokinetic parameters similarly to ritonavir (RTV) in both healthy volunteers and HIV-infected adults. Primary efficacy and safety outcomes of this Phase 3, international, randomized, double-blind, double-dummy, active-controlled trial in HIV-1-infected treatment-naïve adults (GS-US-216-0114/NCT01108510) demonstrated that ATV+COBI was non-inferior to ATV+RTV, each in combination with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), at Weeks 48 and 144, with high rates of virologic success for both regimens (85...
October 21, 2016: Current HIV Research
Mats O Magnusson, Mahesh N Samtani, Elodie L Plan, E Niclas Jonsson, Stefaan Rossenu, An Vermeulen, Alberto Russu
OBJECTIVES: Our objective was to characterize the population pharmacokinetics of paliperidone after intramuscular administration of its long-acting 3-month formulation palmitate ester at various doses and at different injection sites (deltoid and gluteal muscles). METHODS: This retrospective analysis included pooled data from 651 subjects from one phase I study (single injection of the 3-month formulation) and one phase III study (multiple injections of both 1- and 3-month formulations)...
October 14, 2016: Clinical Pharmacokinetics
Julie Fox, Juan M Tiraboschi, Carolina Herrera, Laura Else, Deirdre Egan, Laura Dickinson, Akil Jackson, Natalia Olejniczak, David Back, Saye Khoo, Robin Shattock, Marta Boffito
To investigate the pharmacokinetics/pharmacodynamics of single-dose maraviroc 300 mg in HIV-1 exposure compartments. Maraviroc concentrations in blood, secretions (vaginal, urethral, oral, and rectal), and tissue (vaginal and rectal) were measured, and ex vivo challenge was performed in 54 healthy volunteers to study protection from HIV infection. Maraviroc Cmax occurred within 4 hours in most compartments. Concentrations from 4 to 72 hours were above intracellular (IC) IC90 in all compartments, range 15-8095 ng/mL...
November 1, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Flavia Franconi, Ilaria Campesi
Sex is one of several factors influencing pharmacological responses, but research on its effects on pharmacokinetics and pharmacodynamics, although emerging remarkably, remains poor and contains many methodological issues. In this review, the current state of knowledge about sex differences in pharmacokinetics and some hints to pharmacogenomics were evaluated. Moreover, considering that many pharmacological responses are monitored through biomarkers, the influence of sex on some biomarkers has been reported...
October 3, 2016: Current Medicinal Chemistry
Carmen Belmonte, Dolores Ochoa, Manuel Román, Teresa Cabaleiro, Maria Talegón, Sergio Daniel Sánchez-Rojas, Francisco Abad-Santos
AIMS: The aim of this study was the evaluation of the possible relationship between pharmacokinetics and the safety of aripiprazole as well as its influence on blood pressure (BP), heart rate (HR), and corrected QT (QTc) interval. METHODS: The study population comprised 157 healthy volunteers from 6 bioequivalence clinical trials. Subjects were administered a single 10-mg oral dose of each formulation separated by a 28-day washout period. Plasma concentrations were measured using high-performance liquid chromatography coupled to mass spectrometry...
December 2016: Journal of Clinical Psychopharmacology
Clara Hartmanshenn, Megerle Scherholz, Ioannis P Androulakis
Personalized medicine strives to deliver the 'right drug at the right dose' by considering inter-person variability, one of the causes for therapeutic failure in specialized populations of patients. Physiologically-based pharmacokinetic (PBPK) modeling is a key tool in the advancement of personalized medicine to evaluate complex clinical scenarios, making use of physiological information as well as physicochemical data to simulate various physiological states to predict the distribution of pharmacokinetic responses...
October 2016: Journal of Pharmacokinetics and Pharmacodynamics
Carol Addy, Daniel A Tatosian, Xiaoli S Glasgow, Isaias Noel Gendrano Iii, Christine McCrary Sisk, Eunkyung A Kauh, S Aubrey Stoch, John A Wagner
Omarigliptin is being developed as a potent, once-weekly, oral dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. This double-blind, randomized, placebo-controlled study evaluated the effects of age, sex, and obesity on the pharmacokinetics of omarigliptin in healthy subjects. A single oral dose of omarigliptin 10 mg (n = 6/panel) or placebo (n = 2/panel) was administered in the fasted state to elderly nonobese men and women, young obese (30 ≤ body mass index [BMI] ≤ 35 kg/m(2) ) men and women, and young nonobese women of nonchildbearing potential...
September 2016: Clinical Pharmacology in Drug Development
Sagar Munjal, Anirudh Gautam, Alan M Rapoport, Dennis M Fisher
OBJECTIVE/BACKGROUND: Factors such as body size (weight and body mass index [BMI]), age, sex, and race might influence the clinical response to sumatriptan. We evaluated the impact of these covariates on the plasma concentration (Cp) profile of sumatriptan administered subcutaneously. METHODS: We conducted three pharmacokinetic studies of subcutaneous sumatriptan in 98 healthy adults. Sumatriptan was administered subcutaneously (236 administrations) as either DFN-11 3 mg, a novel 0...
2016: Clinical Pharmacology: Advances and Applications
Cody J Peer, Jonathan D Strope, Shaunna Beedie, Ariel M Ley, Alesia Holly, Karim Calis, Ronald Farkas, Jagan Parepally, Angela Men, Emmanuel O Fadiran, Pamela Scott, Marjorie Jenkins, William H Theodore, Tristan M Sissung
OBJECTIVES: The recommended zolpidem starting dose was lowered in females (5 mg vs. 10 mg) since side effects were more frequent and severe than those of males; the mechanism underlying sex differences in pharmacokinetics (PK) is unknown. We hypothesized that such differences were caused by known sex-related variability in alcohol dehydrogenase (ADH) expression. METHODS: Male, female, and castrated male rats were administered 2.6 mg/kg zolpidem, ± disulfiram (ADH/ALDH pathway inhibitor) to compare PK changes induced by sex and gonadal hormones...
2016: Frontiers in Pharmacology
Yali Shen, Feng Nan, Mei Li, Maozhi Liang, Ying Wang, Zhihui Chen, Zhu Luo
BACKGROUND AND OBJECTIVES: No pharmacokinetic data of intravenous ibuprofen were available in a Chinese population and the published information remained inadequate. The present study aimed to investigate the pharmacokinetic properties of intravenous ibuprofen in healthy Chinese volunteers after single- and multiple-dose administration. METHODS: Twelve subjects received single doses of 200, 400, and 800 mg intravenous ibuprofen, respectively, and multiple doses of 400 mg intravenous ibuprofen, four times per day (every 6 h) till the morning of the sixth day in each study period...
August 23, 2016: Clinical Drug Investigation
K Kubo, M Ohara, M Tachikawa, L H Cavallari, M T M Lee, M S Wen, M G Scordo, E A Nutescu, M A Perera, A Miyajima, N Kaneko, V Pengo, R Padrini, Y T Chen, H Takahashi
Using population pharmacokinetic analysis (PPK), we attempted to identify predictors of S-warfarin clearance (CL(S)) and to clarify population differences in S-warfarin pharmacokinetics among a cohort of 378 African American, Asian and white patients. Significant predictors of CL(S) included clinical (age, body weight and sex) and genotypic (CYP2C9*2,*3 and *8) factors, as well as African American ethnicity, the median CL(S) being 30% lower in the latter than in Asians and whites (170 versus 243 and 250 ml h(-1), P<0...
August 9, 2016: Pharmacogenomics Journal
J D Bergiannaki, P Kostaras
The gender based or gender sensitive pharmacology is a new research area. Differences among sexes are observed in several parameters of their pharmacokinetic which may relate to alteration of their pharmacodynamic as well. Most psychotropics are given per os, and the greater part of their absorption takes place in the small intestine. Premenopausal women have slower gastric emptying times and lower gastrointestinal blood flow which probably reduces the extent of drug absorption. The distribution of drugs is influenced by the relative lower body mass index, the lower blood volume and flow and the greater percentage of body fat of women...
April 2016: Psychiatrikē, Psychiatriki
Peter N Johnson, Jamie L Miller, Tracy M Hagemann, Brady S Moffett
PURPOSE: Inpatient admissions and the top 25 medications for obese pediatric patients at two academic hospitals were assessed. METHODS: Children age 2-17 years were included if they were obese and admitted to either hospital on or after January 1, 2011, and discharged before December 31, 2011. Obesity was defined as a body mass index of ≥95th percentile for age and sex. The objectives of this study were to determine the percentage of hospital admissions involving obese children and compile a list of medications prescribed to these patients...
August 15, 2016: American Journal of Health-system Pharmacy: AJHP
Elisabeth Jünger, Gabriela Gan, Inge Mick, Christian Seipt, Alexandra Markovic, Christian Sommer, Martin H Plawecki, Sean O'Connor, Michael N Smolka, Ulrich S Zimmermann
BACKGROUND: Adolescence is a critical period for the development of alcohol use disorders; drinking habits are rather unstable and genetic influences, such as male sex and a positive family history of alcoholism (FH), are often masked by environmental factors such as peer pressure. METHODS: We investigated how sex and FH modulate alcohol use in a sample of 18- to 19-year-olds from the Dresden Longitudinal Study on Alcohol use in Young Adults. Adolescents reported their real-life drinking in a TimeLine Follow-Back interview...
August 2016: Alcoholism, Clinical and Experimental Research
Miki Nishimura, Mikito Ueda, Junji Saruwatari, Hiroo Nakashima, Naoki Ogusu, Akiko Aoki, Shoko Tsuchimine, Kazuki Matsuda, Kazuma Iwashita, Tatsumasa Ono, Kentaro Oniki, Kazutaka Shimoda, Norio Yasui-Furukori
OBJECTIVE: Although the reduced function of the cytochrome P450 2D6*10 (CYP2D6*10) allele is common among Asian populations, existing evidence does not support paroxetine therapy adjustments for patients who have the CYP2D6*10 allele. In this study, we attempted to evaluate the degree of the impact of different CYP2D6 genotypes on the pharmacokinetic (PK) variability of paroxetine in a Japanese population using a population PK approach. METHODS: This retrospective study included 179 Japanese patients with major depressive disorder who were being treated with paroxetine...
September 2016: Pharmacogenetics and Genomics
Manjunath P Pai
Tedizolid is a novel oxazolidinone antimicrobial administered in its prodrug form, tedizolid phosphate, as a fixed once-daily dose. The pharmacokinetics of tedizolid has been studied in a relatively small proportion of morbidly obese (body mass index [BMI] of ≥40 kg/m(2)) adults through population analyses with sparse sampling. The current study compared the intensively sampled plasma pharmacokinetics of tedizolid phosphate and tedizolid in 9 morbidly obese and 9 age-, sex-, and ideal body weight-matched nonobese (BMI, 18...
August 2016: Antimicrobial Agents and Chemotherapy
Akshanth R Polepally, Prajakta S Badri, Doerthe Eckert, Sven Mensing, Rajeev M Menon
BACKGROUND AND AIMS: Ombitasvir, paritaprevir (given with low-dose ritonavir), and dasabuvir are direct-acting antivirals (DAAs) used with or without ribavirin for the treatment of chronic hepatitis C virus (HCV) infection. The objective of this analysis was to evaluate the effect of renal function as determined by creatinine clearance (CrCL) on the pharmacokinetics of the DAAs, ritonavir, and ribavirin in HCV genotype 1-infected patients with or without cirrhosis. METHODS: Total exposure, measured by area under the plasma concentration-time curve (AUC), was generated for the DAAs, ritonavir, and ribavirin using population pharmacokinetic modeling of data (N = 2093 patients) from 6 Phase 3 studies and 1 Phase 2 study...
May 10, 2016: European Journal of Drug Metabolism and Pharmacokinetics
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