title: Serum Nevirapine and Efavirenz concentrations and effect of concomitant rifampicin in HIV infected children on antiretroviral therapy.
abstract: OBJECTIVE
  To determine factors affecting serum levels of Efavirenz and Nevirapine and analyze the effect of Rifampicin on Nevirapine drug levels.
  
  
  METHODS
  A cross-sectional study was conducted on 30 HIV infected children on Antiretroviral therapy (ART) with Nevirapine or Efavirenz. Patients on simultaneous Rifampicin and Nevirapine were given higher doses of Nevirapine with regular monitoring of liver function tests. Trough levels (before morning dose of Nevirapine) and levels after 2 hours of administration of Nevirapine and levels of Efavirenz were assessed using HPLC and were checked to see if they fall within the therapeutic range.
  
  
  RESULTS
  Thirty patients (14 males) were enrolled in the study with 20 on Nevirapine and 10 (33.3%) on Efavirenz. Seven (23.3%) patients were simultaneously taking rifampicin. The mean Nevirapine dose given to the patients was 350.9±59.8 mg/m2/day (on simultaneous rifampicin) and 309.2±54.6 mg/m2/day (not on concurrent rifampicin). Thirteen (81.3%) of the 16 patients with trough Nevirapine had values in the normal range, 1 (6.3%) had low Nevirapine trough levels and 2 (12.5%) had high Nevirapine trough levels. Of the post 2 hours Nevirapine levels, 1 (5%) had low levels and 3 (15%) had high Nevirapine blood levels. Factors like age (P=0.4, P=0.4087), nourishment (P=0.2679, P=0.4132), ART combination (P=0.4199, P=0.4132), form of the drug (tablet/syrup) (P=0.1964, P=0.4696) or if it was being given as single or in a fixed dose combination (P=0.4179, P=0.4696) and even concurrent rifampicin administration (P=0.284, P=0.472) did not significantly affect the trough and post 2 hours Nevirapine values, respectively. All the five patients being given concurrent rifampicin had normal trough and post 2 hours levels of Nevirapine. The Efavirenz drug levels were 1.9±1.1 g/mL. Of the 10 patients on Efavirenz, 2 (20%) had high and 1 (10%) had low blood levels.
  
  
  CONCLUSIONS
  Concurrent Rifampicin administration does not alter blood levels of Nevirapine; provided the dose of Nevirapine is increased by 20-30%. Formulation of drugs does not alter the blood levels provided drug administered is in the recommended dose.
authors.affiliation: Pediatric HIV Clinic, BJ Wadia Hospital for Children, Mumbai, India. irashah@pediatriconcall.com
authors.forename: Ira
authors.initials: I
authors.lastname: Shah
authors.forename: Soumya
authors.initials: S
authors.lastname: Swaminathan
authors.forename: Geetha
authors.initials: G
authors.lastname: Ramachandran
authors.forename: A K Hemanth
authors.initials: AK
authors.lastname: Kumar
authors.forename: Apurva
authors.initials: A
authors.lastname: Goray
authors.forename: Udit
authors.initials: U
authors.lastname: Chaddha
authors.forename: Swati
authors.initials: S
authors.lastname: Tayal
authors.forename: Mamatha
authors.initials: M
authors.lastname: Lala
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D048588:Benzoxazines / Q000097:blood* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003521:Cyclopropanes; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D008297:Male; D019829:Nevirapine / Q000097:blood* / Q000627:therapeutic use; D012293:Rifampin / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D019829:Nevirapine; C098320:efavirenz; D012293:Rifampin