Steady-State Pharmacokinetics of Nevirapine in HIV-1 Infected Adults in India

Ramachandran, Geetha; Hemanthkumar, Agibothu K.; Rajasekaran, S.; Padmapriyadarsini, Chandrasekaran; Narendran, Gopalan; Suresh, Anitha; Subramanyam, Sudha; Kumaraswami, V.; Swaminathan, Soumya

doi:10.1177/1545109707301344

Cited by 6 publications

(6 citation statements)

References 16 publications

(26 reference statements)

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“…Similar findings with respect to plasma nevirapine levels were observed in a previous study of ours (31). It is of interest that in spite of the concomitant use of EFV and RMP, the peak concentration of EFV was Ͼ4 g/ml in 11 of 19 patients, and no serious adverse events were reported in any of these patients.…”

Section: Discussionsupporting

confidence: 75%

“…Sex is reported to have a modest influence on the pharmacokinetic profiles of certain antiretroviral drugs, including EFV (6,29). A single nucleotide polymorphism at position 516 on the CYP2B6 gene has been widely reported to influence the pharmacokinetics of EFV (3,14,18,19,31,32,33,38,39). India has a large number of HIV-infected individuals, and access to ART is improving.…”

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confidence: 99%

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CYP2B6 G516T Polymorphism but Not Rifampin Coadministration Influences Steady-State Pharmacokinetics of Efavirenz in Human Immunodeficiency Virus-Infected Patients in South India

Ramachandran

Kumar

Rajasekaran

et al. 2009

Antimicrob Agents Chemother

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The dose of efavirenz during concomitant rifampin (RMP) administration is a matter of debate. We studied the influence of RMP coadministration on the steady-state pharmacokinetics of efavirenz in human immunodeficiency virus type 1 (HIV-1)-infected patients in South India. Fifty-seven HIV-tuberculosis (TB)-coinfected and 15 HIV-1-infected patients receiving combination antiretroviral therapy (CART) with an efavirenz (600 mg once daily)-containing regimen were recruited. HIV-TB-coinfected patients were receiving treatment with RMP-containing regimens. A complete pharmacokinetic study was conducted with 19 HIV-TB patients on two occasions (with and without RMP). Trough concentrations of efavirenz were measured in the remaining 38 patients during RMP coadministration. The 15 HIV-infected patients underwent complete pharmacokinetic sampling on one occasion. Plasma efavirenz was estimated by high-performance liquid chromatography, and genotyping of CYP2B6 G516T polymorphism was performed by sequencing. Peak and trough concentrations and exposure to efavirenz were significantly higher in TT than in GT and GG genotype patients (P < 0.001). Although RMP coadministration decreased the peak and trough concentrations and exposure to efavirenz by 17.8, 20.4, and 18.6%, respectively, the differences were not statistically significant. The trough concentration of efavirenz was subtherapeutic (less than 1.0 g/ml) in 6 (8%) of 72 patients. In this South Indian population of HIV-infected patients, CYP2B6 G516T polymorphism but not RMP coadministration significantly influenced the pharmacokinetics of efavirenz; patients with the TT genotype had very high blood levels of efavirenz. While a small proportion of patients had subtherapeutic efavirenz levels, the clinical implications are uncertain, as all had good immunological responses to CART.Tuberculosis (TB) remains one of the most important opportunistic infections in human immunodeficiency virus (HIV)-infected individuals. The burden of effectively treating HIV-TB-coinfected patients is a well-recognized global public health problem. A decreased risk of death has been observed in patients starting combination antiretroviral therapy (CART) compared with those not receiving CART after the diagnosis of TB (2, 9, 13). In India, there are effective treatments available for both HIV disease and TB through the government program. Concomitant administration of CART and anti-TB medications is often complicated because of drug-drug interactions and the adverse-effect profile (17,30,36).Efavirenz (EFV) is a potent nonnucleoside reverse transcriptase inhibitor for the treatment of HIV type 1 (HIV-1) infection. EFV has been recommended as a first-line option in antiretroviral therapy (ART) and the preferential choice in TB-and HIV-coinfected patients, despite induction of the cytochrome P-450 system by rifampin (RMP). The available pharmacokinetic data provide evidence of a 13 to 25% reduction in EFV levels when it is coadministered with RMP (20), which is lower than those of nevirapine (40...

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Section: Discussionsupporting

confidence: 75%

mentioning

confidence: 99%

CYP2B6 G516T Polymorphism but Not Rifampin Coadministration Influences Steady-State Pharmacokinetics of Efavirenz in Human Immunodeficiency Virus-Infected Patients in South India

Ramachandran

Kumar

Rajasekaran

et al. 2009

Antimicrob Agents Chemother

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“…The normal range for random blood sugar was considered as 80–140 mg/dl as per kit instructions [28].…”

Section: Methodsmentioning

confidence: 99%

“…Random plasma glucose levels were measured by GOD-POD method using Olympus AU 400 auto analyzer (Olympus GmbH, Hamburg, Germany) with Olympus reagents. The normal range for random blood sugar was considered as 80–140 mg/dl as per kit instructions [28] .…”

Section: Methodsmentioning

confidence: 99%

Role of QuantiFERON-TB Gold, Interferon Gamma Inducible Protein-10 and Tuberculin Skin Test in Active Tuberculosis Diagnosis

et al. 2010

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BackgroundThe measurement of Interferon gamma or Interferon gamma inducible protein (IP)-10 in antigen stimulated blood samples is suggested as an alternative method for latent tuberculosis (TB) diagnosis. Nonetheless, their role in active TB diagnosis, particularly in TB endemic settings is yet to be defined. In this study, the sensitivities and specificities of Interferon gamma release assay (IGRA), IP-10 assay and tuberculin skin test (TST) in detecting active TB cases were assessed in human immunodeficiency virus (HIV) sero-negative TB patients and healthy controls respectively.Methods/Principal FindingsA total of 177 adult TB patients and 100 healthy controls were included for this study. QuantiFERON-TB Gold In-tube (QFT-IT) method was used to analyze the sensitivity and specificity of IGRA. QFT-IT, IP-10 and TST yielded the diagnostic sensitivities of 90.6% (95%CI: 86.3%–94.9%), 92.5% (95%CI: 88.6%–96.4%) and 68.9% (95%CI: 60.6%–77.2%) and specificities of 55% (95% CI: 35.2%–54.8%), 48% (95% CI: 38.2%–57.8%) and 75.5% (95% CI: 66.8%–84.2%), respectively. The extent of pulmonary involvement or presence of diabetes mellitus did not appear to influence the sensitivities of any of these tests. The combination of any of the two tests among QFT-IT, IP-10 and TST showed >98% sensitivity among smear negative cases and particularly the combination of IP-10, TST and smear microscopy showed 100% sensitivity, however, the specificity was decreased to 44.8%.Conclusions/SignificanceQFT-IT and IP-10 were highly sensitive in detecting active TB cases. The combination with TST improved the sensitivity of QFT-IT and IP-10 significantly. Although the higher sensitivity of combination of QFT-IT/IP-10 and TST may be useful in active TB diagnosis, they are limited by their poor specificity due to the high prevalence of latent TB in our settings.

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“…The potential threshold trough concentration of NVP in plasma is ~3.0 μg/ml . A comparison of the steady‐state pharmacokinetics of NVP is presented in Table …”

Section: Resultsmentioning

confidence: 99%

A Review of Clinical Pharmacokinetic and Pharmacodynamic Profiles of Select Antiretrovirals: Focus on Differences among Chinese Patients

Ma³

et al. 2019

Pharmacotherapy

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OBJECTIVE To identify the pharmacokinetic differences of antiretroviral drugs between HIV-infected Chinese patients and patients of other race/ethnicities. STUDY DESIGN Results from prospective, open-label pharmacokinetic studies among Chinese and historical data from other race/ethnicities. PATIENTS Pharmacokinetics of six commonly used antiretroviral drugs, including zidovudine, lamivudine, tenofovir disoproxil fumarate, nevirapine, efavirenz and lopinavir/ritonavir, was evaluated in HIV-infected Chinese patients and compared with historical data from other race/ethnicities. ANALYSIS Pharmacokinetic analyses were performed at the steady state among HIV-infected Chinese patients. Safety data were collected during the follow-up. The pharmacokinetic parameters including maximal concentrations (Cmax), area-under-curve (AUC) and clearance (Cl/F) from the Chinese patients were compared to the historic data from other race/ethnicities. RESULTS Current evidence, though limited, suggested that these antiretroviral agents were generally safe and effective among HIV-infected Chinese patients. However, compared with other racial groups, Chinese patients exhibited higher C max , AUC and lower Cl/F for most of the agents, and the incidences of adverse reactions, for example, liver toxicity, rash, and bone health, were more frequent. CONCLUSIONS These pharmacokinetic differences suggest that lower dosages for commonly prescribed antiretroviral drugs in China might be appropriate to reduce drug-related adverse reactions, while maintain the antiviral efficacy.

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Steady-State Pharmacokinetics of Nevirapine in HIV-1 Infected Adults in India

Cited by 6 publications

References 16 publications

CYP2B6 G516T Polymorphism but Not Rifampin Coadministration Influences Steady-State Pharmacokinetics of Efavirenz in Human Immunodeficiency Virus-Infected Patients in South India

CYP2B6 G516T Polymorphism but Not Rifampin Coadministration Influences Steady-State Pharmacokinetics of Efavirenz in Human Immunodeficiency Virus-Infected Patients in South India

Role of QuantiFERON-TB Gold, Interferon Gamma Inducible Protein-10 and Tuberculin Skin Test in Active Tuberculosis Diagnosis

A Review of Clinical Pharmacokinetic and Pharmacodynamic Profiles of Select Antiretrovirals: Focus on Differences among Chinese Patients

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