Pharmacokinetic interactions between depot medroxyprogesterone acetate and combination antiretroviral therapy

Nanda, Kavita; Amaral, Eliana; Hays, Melissa; Viscola, Marco Aurélio Martino; Mehta, Neha; Bahamondes, Luís

doi:10.1016/j.fertnstert.2007.07.1348

Cited by 58 publications

(55 citation statements)

References 16 publications

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“…The described method is appropriate for quantification of MPA in plasma and can be used in investigations for understanding potential drug-drug interactions between MPA and other concomitant medications (11,23). This is an area of interest, since drug-drug interactions may significantly affect drug pharmacokinetics.…”

Section: Discussionmentioning

confidence: 99%

“…Further, ongoing clinical studies by our group are aimed at evaluating the potential interaction of MPA with antiretroviral agents that are used for pre-exposure prophylaxis. Characterization of potential drugdrug interactions in this example is important in ensuring not only proper contraceptive protection, but also sufficient antiretroviral therapeutic efficacy (11,24). Additionally, the use of DMPA vs oral formulations may influence compound pharmacokinetics and pharmacodynamics in the back-…”

Section: Discussionmentioning

confidence: 99%

“…For IM DMPA injections, there was a study that assessed the pharmacokinetics after an IM injection of DMPA containing 150 g/L of drug, in which the concentration of MPA peaked at 2.5 ng/mL after approximately 14 days. The MPA drug concentrations fell below 1 ng/mL 56 days post-DMPA injection (11). A recent analysis evaluated the MPA concentrations in women who received a subcutaneous (104 mg/0.65 mL drug) injection in the upper arm.…”

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confidence: 99%

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Rapid Quantification of Medroxyprogesterone Acetate (MPA) in Human Plasma by LC-MS/MS

Hummert

Manohar

Aung

et al. 2016

The Journal of Applied Laboratory Medicine

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Background: Medroxyprogesterone acetate (MPA) is a common contraceptive agent taken both orally and as a subcutaneous or intramuscular injection. Current LC-MS/MS methods for MPA quantification require large sample volumes and low-throughput analytical run times. Therefore, there are opportunities to improve upon existing methods for MPA quantification. Methods: MPA was extracted from 600 μL plasma, evaporated to dryness, and the reconstituted solution was injected onto a Waters Acquity liquid chromatography (LC) system via an Agilent Zorbax Eclipse-Plus C18 2.1 × 50 mm (5.0 μm) column. MPA and its internal standard were monitored on a QTRAP ® 5500 mass analyzer operated in positive ionization mode. The method was validated according to the Food and Drug Administration Bioanalytical Method Validation guidelines. Results:The analytical measuring range of the assay was 200 -10 000 pg/mL. QC samples prepared at the lower limit of quantification (LLOQ; 200 pg/mL) and low (600 pg/mL), mid (1750 pg/mL), and high (8500 pg/mL) levels showed interassay precision and accuracy ≤15.2% and ≤±9.6%, respectively. Stability-challenged samples yielded ≤15% from freshly prepared samples. Dilutional and matrix effects studies were also acceptable. The assay was also assessed in participants prescribed depot medroxyprogesterone acetate; observed concentrations were within the dynamic range of the assay. Conclusions: An LC-MS/MS method for the quantification of MPA in plasma has been developed and validated. The described method is sufficiently sensitive and robust to quantify MPA in plasma and meets the criteria to support clinical trials.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Rapid Quantification of Medroxyprogesterone Acetate (MPA) in Human Plasma by LC-MS/MS

Hummert

Manohar

Aung

et al. 2016

The Journal of Applied Laboratory Medicine

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“…The metabolism of DMPA is through the liver; therefore, it is not recommended for those with active liver disease. [39][40][41] …”

Section: Combined Hormonal Contraceptivesmentioning

confidence: 99%

“…41 The effectiveness is > 99%, and the protection lasts for 3 years. On removal, the etonogestrel drops rapidly, with most patients ovulating after 3 weeks.…”

Section: Etonogestrel Implantmentioning

confidence: 99%

Untitled

Yousif

Bridson

Halawa³

2016

Exp Clin Transplant

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There is a misconception among transplant clinicians that contraception after a successful renal transplant is challenging. This is partly due to the complex nature of transplant patients, where immunosuppression and graft dysfunction create major concerns. In addition, good evidence regarding contraception and transplant is scarce, with most of the evidence extrapolated from observational and case-controlled studies, thus adding to the dilemma of treating these patients. In this review, we closely analyzed the different methods of contraception and critically evaluated the efficacy of the different options for contraception after kidney transplant. We conclude that contraception after renal transplant is successful with acceptable risk. A multidisciplinary team approach involving obstetricians and transplant clinicians to decide the appropriate timing for conception is recommended. Early counseling on contraception is important to reduce the risk of unplanned pregnancies, improve pregnancy outcomes, and reduce maternal complications in patients after kidney transplant. To ascertain appropriate advice on the method of contraception, individualizing the method of contraception according to a patient's individual risks and expectations is essential.

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A Semimechanistic Pharmacokinetic Model for Depot Medroxyprogesterone Acetate and Drug–Drug Interactions With Antiretroviral and Antituberculosis Treatment

Francis

Mngqibisa

McIlleron

et al. 2021

Clin Pharma and Therapeutics

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Depot medroxyprogesterone acetate (DMPA) is an injectable hormonal contraceptive, widely used by women of childbearing potential living with HIV and/or tuberculosis. As medroxyprogesterone acetate (MPA) is a CYP3A4 substrate, drug-drug interactions (DDIs) with antiretroviral or antituberculosis treatment may lead to subtherapeutic MPA concentrations (<0.1 ng/mL), resulting in contraception failure, when DMPA is dosed at 12week intervals. A pooled population pharmacokinetic analysis with 744 plasma MPA concentrations from 138 women treated with DMPA and antiretroviral/antituberculosis treatment across three clinical trials was performed. Monte Carlo simulations were performed to predict the percentage of participants with subtherapeutic MPA concentrations and to derive alternative dosing strategies. MPA clearance increased by 24.7% with efavirenz co-administration. Efavirenz plus antituberculosis treatment (rifampicin+isoniazid) increased clearance by 52.4%. Conversely, lopinavir/ritonavir and nelfinavir decreased clearance (28.7% Accepted ArticleThis article is protected by copyright. All rights reserved and 15.8%, respectively), but lopinavir/ritonavir also accelerated MPA's appearance into the systemic circulation, thus shortening the terminal half-life. A higher risk of subtherapeutic MPA concentrations at week 12 was predicted on a typical 60-kg woman on efavirenz (4.99%) and efavirenz with antituberculosis treatment (6.08%) when compared to MPA alone (2.91%).This risk increased in women with higher body weight. Simulations show that re-dosing every 8-10 weeks circumvents the risk of subtherapeutic MPA exposure associated with these DDIs. Dosing DMPA every 8-10 weeks should eliminate the risk of subtherapeutic MPA exposure caused by co-administered efavirenz and/or antituberculosis treatment, thus reducing the risk of contraceptive failure. Main text

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Pharmacokinetic interactions between depot medroxyprogesterone acetate and combination antiretroviral therapy

Cited by 58 publications

References 16 publications

Rapid Quantification of Medroxyprogesterone Acetate (MPA) in Human Plasma by LC-MS/MS

Rapid Quantification of Medroxyprogesterone Acetate (MPA) in Human Plasma by LC-MS/MS

Untitled

A Semimechanistic Pharmacokinetic Model for Depot Medroxyprogesterone Acetate and Drug–Drug Interactions With Antiretroviral and Antituberculosis Treatment

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