Population Pharmacokinetics of Isoniazid, Pyrazinamide, and Ethambutol in Pregnant South African Women with Tuberculosis and HIV

ABSTRACT Tuberculosis is an important cause of maternal morbidity, but little is known about the effects of pregnancy on antituberculosis drug concentrations. We developed population pharmacokinetic models to describe drug dispositions of isoniazid, pyrazinamide, and ethambutol in pregnant women with tuberculosis and HIV. HIV-positive pregnant women with tuberculosis receiving standard first-line tuberculosis treatment and participating in Tshepiso, a prospective cohort study in Soweto, South Africa, underwent sparse pharmacokinetic sampling at >36 weeks of gestation and 7 weeks postpartum. The effects of pregnancy on the pharmacokinetics of isoniazid, pyrazinamide, and ethambutol were investigated via population pharmacokinetic modeling. Isoniazid, pyrazinamide, and ethambutol concentrations were available for 29, 18, and 18 women, respectively. Their median weight was 66 kg while pregnant and 64 kg postpartum. No significant differences were observed in drug clearance, volume of distribution, or bioavailability during and after pregnancy. The model-estimated isoniazid, pyrazinamide, and ethambutol area under the concentration-time curve from 0 to 24 h (AUC0–24) medians were, respectively, 6.88, 419, and 16.5 mg · h/liter during pregnancy versus 5.01, 407, and 19.0 mg · h/liter postpartum. The model-estimated maximum concentration (Cmax) medians for isoniazid, pyrazinamide, and ethambutol were, respectively, 1.39, 35.9, and 1.82 mg/liter during pregnancy versus 1.43, 34.5, and 2.11 mg/liter postpartum. A posteriori power calculations determined that our analysis was powered 91.8%, 59.2%, and 90.1% at a P of <0.01 to detect a 40% decrease in the AUCs of isoniazid, pyrazinamide, and ethambutol, respectively. Pregnancy does not appear to cause relevant changes in the exposure to isoniazid, pyrazinamide, and ethambutol. Additional studies of antituberculosis drugs in pregnancy are needed.

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Didanosine Population Pharmacokinetics in West African Human Immunodeficiency Virus-Infected Children Administered Once-Daily Tablets in Relation to Efficacy after One Year of Treatment

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01187-08 ◽

2009 ◽

Vol 53 (10) ◽

pp. 4399-4406 ◽

Cited By ~ 8

Author(s):

Déborah Hirt ◽

Christophe Bardin ◽

Serge Diagbouga ◽

Boubacar Nacro ◽

Hervé Hien ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Viral Load ◽

Compartment Model ◽

Volume Of Distribution ◽

Wilcoxon Test ◽

Population Pharmacokinetic ◽

Time Curve ◽

Drug Concentrations ◽

Immunodeficiency Virus ◽

One Year

ABSTRACT Our objective was to study didanosine pharmacokinetics in children after the administration of tablets, the only formulation available in Burkina Faso for which data are missing, and to establish relationships between doses, plasma drug concentrations, and treatment effects (efficacy/toxicity). Didanosine concentrations were measured for 40 children after 2 weeks and for 9 children after 2 to 5 months of treatment with a didanosine-lamivudine-efavirenz combination. A population pharmacokinetic model was developed with NONMEM. The link between the maximal concentration of the drug in plasma (C max), the area under the concentration-time curve (AUC), and the decrease in human immunodeficiency virus (HIV) type 1 RNA levels after 12 months of treatment was evaluated. The threshold AUC that improved efficacy was determined by the use of a Wilcoxon test for HIV RNA, and an optimized dosing schedule was simulated. Didanosine pharmacokinetics was best described by a one-compartment model with first-order absorption and elimination. The apparent clearance and volume of distribution were higher for tablets, probably due to a lower bioavailability with tablets than with pediatric powder. The decrease in the viral load after 12 months of treatment was significantly correlated with the didanosine AUC and C max (P ≤ 0.02) during the first weeks of treatment. An AUC of >0.60 mg/liter·h was significantly linked to a greater decrease in the viral load (a decrease of 3 log10 versus 2.4 log10 copies/ml; P = 0.03) than that with a lower AUC. A didanosine dose of 360 mg/m2 administered as tablets should be a more appropriate dose than 240 mg/m2 to improve efficacy for these children. However, data on adverse events with this dosage are missing.

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Pharmacokinetics of Anidulafungin in Obese and Normal-Weight Adults

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00063-18 ◽

2018 ◽

Vol 62 (7) ◽

Cited By ~ 6

Author(s):

Roeland E. Wasmann ◽

Rob ter Heine ◽

Eric P. van Dongen ◽

David M. Burger ◽

Vincent J. Lempers ◽

...

Keyword(s):

Reference Value ◽

Total Body Weight ◽

Volume Of Distribution ◽

Normal Weight ◽

Pharmacokinetic Parameters ◽

Morbidly Obese ◽

Population Pharmacokinetic ◽

Time Curve ◽

Population Pharmacokinetic Modeling ◽

Obese Subjects

ABSTRACT In 2025, approximately one out of five adults will be obese. Physiological changes associated with obesity have been shown to influence the pharmacokinetics of drugs. Anidulafungin is frequently used in critically ill patients, and to achieve optimal efficacy, it is essential that its dose is appropriate for each patient's characteristics. We combined data from obese subjects with data from normal-weight subjects and determined an optimal dosing regimen for obese patients by population pharmacokinetic modeling. Twenty adults, 12 of which were normal-weight healthy subjects (median weight, 67.7 kg; range, 61.5 to 93.6 kg) and 8 of which were morbidly obese subjects (median weight, 149.7 kg; range, 124.1 to 166.5 kg) were included in the analysis. Subjects received a single dose of 100 mg anidulafungin intravenously over 90 min, upon which blood samples were obtained. Monte Carlo simulations were performed to optimize dosing in obesity. A three-compartment model and equal volumes of distribution described the data best. Total body weight was identified as a descriptor for both clearance and the volume of distribution, but the effect of weight on these parameters was limited. Simulations showed that with the licensed 100-mg dose, more than 97% of subjects with a weight above 140 kg will have an area under the concentration-time curve from 0 to 24 h of less than 99 mg · h/liter (the reference value for normal-weight individuals). We found that in obese and normal-weight subjects, weight influenced both of the anidulafungin pharmacokinetic parameters clearance and volume of distribution, implying a lower exposure to anidulafungin in (morbidly) obese individuals. Consequently, a 25% increase in the loading and maintenance doses could be considered in patients weighing more than 140 kg.

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Are South African Mothers Moving? Patterns and Correlates of Physical Activity and Sedentary Behavior in Pregnant Black South African Women

Journal of Physical Activity and Health ◽

10.1123/jpah.2016-0388 ◽

2017 ◽

Vol 14 (5) ◽

pp. 329-335 ◽

Cited By ~ 7

Author(s):

Estelle D. Watson ◽

Mireille N. M. Van Poppel ◽

Rachel A. Jones ◽

Shane A Norris ◽

Lisa K. Micklesfield

Keyword(s):

Physical Activity ◽

Pregnant Women ◽

South African ◽

African Women ◽

Activity Levels ◽

Second Trimester ◽

Recreational Physical Activity ◽

Third Trimester ◽

Black South African ◽

South African Women

Background:Although physical activity during pregnancy may be beneficial, the prenatal period is a vulnerable time for decreasing physical activity levels and increasing sedentary time.Methods:This longitudinal cohort study measured physical activity using the Global Physical Activity Questionnaire (GPAQ) in singleton, pregnant women in the second (14–18 wk gestation; n = 332) and third trimester (29–33 wk; n = 256).Results:There was a significant decrease in total MVPA (MET mins/wk) between the second and third trimester (P = .01). The majority of physical activity time was spent in walking for transport (80%), and less than 2% in recreational activities. In both trimesters, being married was inversely associated with walking for transport (second trimester: β = –0.12 95% CI = –0.31 to –0.02, third trimester: β = –0.17 95% CI = –0.47 to –0.07) and owning a car was positively associated with recreational physical activity (second trimester: β = 0.16 95% CI = 0.02 to 0.32, third trimester: β = 0.17 95% CI = 0.04 to 0.27). The women spent an average of 5 hours per day sitting.Conclusions:The low and declining levels of physical activity during pregnancy in this population are a concern. Interventions that include lifestyle education and provision of accessible recreational physical activity programs for pregnant women are needed.

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BREAST SELF-EXAMINATION AND CERVICAL (PAP) SMEAR TEST: ATTITUDES AND SELF-REPORTED PRACTICES AMONG SOUTH AFRICAN WOMEN

Psychological Reports ◽

10.2466/pr0.89.5.27-32 ◽

2001 ◽

Vol 89 (5) ◽

pp. 27

Author(s):

KARL PELTZER

Keyword(s):

South African ◽

Pap Smear ◽

African Women ◽

Breast Self Examination ◽

Pap Smear Test ◽

Smear Test ◽

South African Women ◽

Self Examination

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THE SINS OF THE FATHER: GENDER- BASED VIOLENCE IN POST-APARTHEID SOUTH AFRICA

Commonwealth Youth and Development ◽

10.25159/1727-7140/1798 ◽

2017 ◽

Vol 14 (2) ◽

pp. 57-70 ◽

Cited By ~ 1

Author(s):

Lyn Snodgrass

Keyword(s):

South Africa ◽

Black Women ◽

South African ◽

African Women ◽

Gender Based Violence ◽

Political Issues ◽

Race And Gender ◽

Gender Based ◽

And Gender ◽

South African Women

This article explores the complexities of gender-based violence in post-apartheid South Africa and interrogates the socio-political issues at the intersection of class, ‘race’ and gender, which impact South African women. Gender equality is up against a powerful enemy in societies with strong patriarchal traditions such as South Africa, where women of all ‘races’ and cultures have been oppressed, exploited and kept in positions of subservience for generations. In South Africa, where sexism and racism intersect, black women as a group have suffered the major brunt of this discrimination and are at the receiving end of extreme violence. South Africa’s gender-based violence is fuelled historically by the ideologies of apartheid (racism) and patriarchy (sexism), which are symbiotically premised on systemic humiliation that devalues and debases whole groups of people and renders them inferior. It is further argued that the current neo-patriarchal backlash in South Africa foments and sustains the subjugation of women and casts them as both victims and perpetuators of pervasive patriarchal values.

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