Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers

Ouellet, Danièle; Hsu, Ann; Qian, Jiang; Locke, Charles; Eason, Carolyn J.; Cavanaugh, John H.; Leonard, John M.; Granneman, G. Richard

doi:10.1046/j.1365-2125.1998.00749.x

Cited by 161 publications

(100 citation statements)

References 25 publications

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“…This role of estrogen and ERα is critical for the prevention of atherosclerosis induced by HIV protease inhibitors. This may be of particular importance in patients as HIV and HIV protease inhibitor therapy can alter gonadal hormone levels as well as the metabolism of estrogen (17,37). Alterations in endogenous estrogen levels may contribute to the loss of the protection against cardiovascular disease in females on HIV protease inhibitor therapy.…”

Section: Discussionmentioning

confidence: 99%

Estrogen Receptor-α Mediates Gender Differences in Atherosclerosis Induced by HIV Protease Inhibitors

Allred

Smart

Wilson

2006

Journal of Biological Chemistry

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As part of highly active antiretroviral therapy, protease inhibitor treatment has significantly increased the lifespan of HIV infected individuals. Many patients, however, develop negative side effects including premature atherosclerosis. We have previously demonstrated that in male low-density lipoprotein receptor (LDL-R) null mice, HIV protease inhibitors induce atherosclerotic lesions and cholesterol accumulation in macrophages in the absence of changes in plasma lipid levels. We determined that these increases were due to an up-regulation of the scavenger receptor, CD36. In the present study, we examined the effects of HIV protease inhibitors in female LDL-R null mice. Female mice given ritonavir and amprenavir (23 and 10 μg/mouse/day, respectively) developed fewer atherosclerotic lesions than males. Furthermore, peritoneal macrophages isolated from ritonavirtreated females had reduced levels of cholesterol accumulation as compared to males, and CD36 protein levels were increased to a significantly lesser degree in females than in males. To investigate the molecular mechanisms of this gender difference, we examined the effect of genetically removing estrogen receptor-alpha (ERα). In female mice lacking both LDL-R and ERα, the protective effect of gender was lost. Additionally, the reduced levels of cholesterol accumulation in macrophages observed in females was reversed. Furthermore, the absence of ERα resulted in increased expression of CD36 protein in a macrophage-specific manner in mice treated with ritonavir. These data demonstrate that ERα is directly involved in the regulation of cholesterol metabolism in macrophages and plays an important role in the gender differences observed in HIV protease inhibitor-induced atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Estrogen Receptor-α Mediates Gender Differences in Atherosclerosis Induced by HIV Protease Inhibitors

Allred

Smart

Wilson

2006

Journal of Biological Chemistry

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“…Ritonavir reduces the efficacy of hormone-based birth control [20,21] . The PEARL study protocols have required that women participating in the trials avoid pregnancy by using at least two forms of birth control, neither of which can be hormone-based.…”

Section: Ombitasvir-paritaprevir-ritonavir and Dasabuvir: Psychosociamentioning

confidence: 99%

Psychosocial assessment and monitoring in the new era of non-interferon-alpha hepatitis C virus treatments

Rowan¹

2015

WJH

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sofosbuvir regimen and the ombitasvir/paritaprevir/ ritonavir and dasabuvir regimen, we may now be in the era of all-pill regimens for HCV. Until this development, interferon-alpha along with Ribavirin has remained part of the standard of care for HCV patients. That regimen necessitates psychosocial assessment of factors affecting treatment eligibility, including interferon-alpharelated depressive symptoms, confounding psychiatric conditions, and social aspects such as homelessness affecting treatment eligibility. These factors have delayed as much as 70% of otherwise eligible candidates from interferon-based treatment, and have required treating physicians to monitor psychiatric as well as medical side effects throughout treatment. Allpill DAA regimens with the efficaciousness that would preclude reliance upon interferon-alpha or ribavirin have been anticipated for years. Efficacy studies for these recently approved DAA regimens provide evidence to assess the degree that psychosocial assessment and monitoring will be required. With shorter treatment timelines, greatly reduced side effect profiles, and easier regimens, psychosocial contraindications are greatly reduced. However, current or recent psychiatric comorbidity, and drug-drug interactions with psychiatric drugs, will require some level of clinical attention. Evidence from these efficacy studies tentatively demonstrate that the era of needing significant psychosocial assessment and monitoring may be at an end, as long as a manageable handful of clinical issues are managed. Author contributions: Rowan PJ conceived the study plan, identified data sources, analyzed data, drafted the manuscript, and approved the final version; Bhulani N sought and identified relevant data for analysis per plan, contributed to analysis of data, contributed to drafting the manuscript, and approved the final version. Conflict-of-interest statement:The authors have no conflicts of interest. Psychosocial assessment and monitoring in the new era of non-interferon-alpha hepatitis C virus treatments thus far seem to have short treatment timelines and relatively benign side effect profiles. Depression has not emerged as a side effect of these treatments. With efficacious regimens that include no interferon-alpha and no ribavirin, there may no longer be a need for strong psychosocial assessment and monitoring built into the routine of HCV treatment. Good history-taking, strong pharmaceutical review, and reliable consultative relationships should be adequate for meeting psychosocial needs in HCV treatment.Rowan PJ, Bhulani N. Psychosocial assessment and monitoring in the new era of non-interferon-alpha hepatitis C virus treatments. World

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“…While the significant elevations in the simvastatin and atorvastatin levels are explained by their dependency as substrates for the CYP3A4 isoenzyme, the mechanism for the reductions in pravastatin concentrations are not currently known. It has been speculated that since pravastatin is metabolized via glucuronidation and sulfation, the inducing properties of RTV on the glucuronidation pathway may be potentially contributing to this drug interaction [16]. Unfortunately, this pharmacokinetic study did not report the lipid lowering effects of any of the statins studies, thus it could not be determined if there was an attenuation of the LDL lowering with pravastatin.…”

Section: Pi-based ---------------------------------------------------mentioning

confidence: 42%

Efficacy of Pravastatin in Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) and Protease Inhibitor (PI)-based HAART in HIV-Infected Patients

Eaton¹,

Rahman²,

Nguyen³

et al. 2008

American J. of Infectious Diseases

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Pravastatin has generally been considered a safe and effective option for HIV-infected patients on highly active antiretroviral therapy (HAART). However, pravastatin concentrations are known to significantly decrease with concomitant efavirenz (EFV) use. Currently there are no studies determining if these reductions in pravastatin possibly translate into an attenuation of its lipid lowering efficacy when used in HIV-infected patients on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART. To evaluate the differences in the lipid lowering efficacy of pravastatin for the treatment of dyslipidemia in HIV-infected patients on NNRTI-based HAART compared to protease inhibitor (PI)-based regimens. A single center, retrospective evaluation of a comprehensive electronic HIV registry that identified HIV-infected, Veterans Affairs (VA) patients who received pravastatin 20 mg plus NNRTI or PI-based HAART from January 1997 to November 2006 who met the strict criteria for inclusion. A total of 18 patients [NNRTI (n = 7) and PI (n = 11)] met the strict criteria for inclusion. In HIV-infected patients taking NNRTI-based HAART there was a reduction in TC by -10.1%, LDL by -12% and non-HDL by -12.2% within 6 months after starting pravastatin 20 mg. In HIVinfected patients taking PI-based HAART, there was a reduction in TC by -10.1%, in LDL by -21.1% and in non-HDL by -13.8% within 6 months after starting pravastatin 20 mg. In both groups, only one additional patient achieved their patient specific lipid goals. In either group these reductions were seen without any apparent adverse drug events or compromise to virologic or immunologic control. This initial evaluation suggests that pravastatin's efficacy may be attenuated with NNRTIs versus PI-based HAART, possibly due to known reductions in pravastatin concentrations when administered with NNRTI-based regimens. These effects were seen without any apparent compromises to safety and should be validated in a prospective study.

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Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers

Cited by 161 publications

References 25 publications

Estrogen Receptor-α Mediates Gender Differences in Atherosclerosis Induced by HIV Protease Inhibitors

Estrogen Receptor-α Mediates Gender Differences in Atherosclerosis Induced by HIV Protease Inhibitors

Psychosocial assessment and monitoring in the new era of non-interferon-alpha hepatitis C virus treatments

Efficacy of Pravastatin in Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) and Protease Inhibitor (PI)-based HAART in HIV-Infected Patients

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