Pharmacokinetic-pharmacodynamic modelling of atazanavir in hair among adolescents on antiretroviral treatment in Zimbabwe

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dc.contributor.authorNgara, Bernarden_ZA
dc.contributor.authorZvada, Simbarasheen_ZA
dc.contributor.authorChawana, Tariro D.en_ZA
dc.contributor.authorNhachi, Charles F. B.en_ZA
dc.contributor.authorRusakaniko, Simbarasheen_ZA
dc.date.accessioned2021-08-19T06:36:16Z
dc.date.available2021-08-19T06:36:16Z
dc.date.issued2021-05-24
dc.date.updated2021-05-30T04:21:51Z
dc.descriptionCITATION: Ngara, B., et al. 2021. Pharmacokinetic-pharmacodynamic modelling of atazanavir in hair among adolescents on antiretroviral treatment in Zimbabwe. BMC Pharmacology and Toxicology, 22:29, doi:10.1186/s40360-021-00497-8.
dc.descriptionThe original publication is available at https://bmcpharmacoltoxicol.biomedcentral.com
dc.description.abstractBackground: Drug potency is a pharmacological parameter defining dose or concentration of drug required to obtain 50% of the drug’s maximal effect. Pharmacokinetic-pharmacodynamic modelling and simulation allows estimation of potency and evaluate strategies improving treatment outcome. The objective of our study is to determine potency of atazanavir in hair, defined as atazanavir level in hair associated with 50% probability of failing to achieve viral load below 1000 copies/ml among adolescents, and explore the effect of participant specific variables on potency. Methods: A secondary analysis was performed on data from a previous study conducted in HIV-infected adolescents failing 2nd line ART from Harare central hospital, Zimbabwe, between 2015 and 2016. We simulated atazanavir concentrations in hair using NONMEM (version 7.3) ADVAN 13, based on a previously established pharmacokinetic model. Logistic regression methods were used for PKPD analysis. Simulations utilising PKPD model focused on estimation of potency and exploring the effect of covariates. Results: The potency of atazanavir in hair was found to be 4.5 ng/mg hair before adjusting for covariate effects. Participants at three months follow-up, reporting adequate adherence, having normal BMI-for-age, and cared for by mature guardians had increased potency of atazanavir in hair of 2.6 ng/mg, however the follow-up event was the only statistically significant factor at 5% level. Conclusion: Atazanavir in hair in the range 2.6 to 4.5 ng/mg is associated with above 50% probability of early viral load suppression. Adherence monitoring to adolescents with lower potency of atazanavir is recommended. The effect self-reported adherence level, BMI-for-age, and caregiver status require further evaluation.
dc.description.urihttps://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-021-00497-8
dc.description.versionPublisher's version
dc.format.extent12 pagesen_ZA
dc.identifier.citationNgara, B., et al. 2021. Pharmacokinetic-pharmacodynamic modelling of atazanavir in hair among adolescents on antiretroviral treatment in Zimbabwe. BMC Pharmacology and Toxicology, 22:29, doi:10.1186/s40360-021-00497-8
dc.identifier.issn2050-6511 (online)
dc.identifier.otherdoi:10.1186/s40360-021-00497-8
dc.identifier.urihttp://hdl.handle.net/10019.1/110880
dc.language.isoen_ZAen_ZA
dc.publisherBMCen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectPharmacodynamicsen_ZA
dc.subjectAtazanaviren_ZA
dc.subjectPharmacokineticsen_ZA
dc.subjectAntiretroviral drugs -- Zimbabween_ZA
dc.subjectAdolescentsen_ZA
dc.subjectHair -- Analysisen_ZA
dc.titlePharmacokinetic-pharmacodynamic modelling of atazanavir in hair among adolescents on antiretroviral treatment in Zimbabween_ZA
dc.typeArticleen_ZA
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