Pharmacokinetic Interactions Between Buprenorphine and Kaletra (Lopinavir/Ritonavir)
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional

Summary: 
      The main purpose of this protocol is to study the effect of an HIV medication, Kaletra
      (lopinavir/ritonavir), on buprenorphine in non-HIV infected people who have been receiving
      the same dose of buprenorphine for at least 3 weeks.

      Study Hypothesis:

      Kaletra (lopinavir/ritonavir) will increase buprenorphine plasma levels without any
      significant clinical effect on the subject or need for dose adjustment.
    

Detailed description: 
      Buprenorphine (BUP) is a partial opiate agonist dosed sublingually for both supervised opiate
      withdrawal and maintenance for opiate dependence. Until recently, methadone has been the
      mainstay of pharmacological treatment for opiate-dependent persons with HIV infection. In
      October, 2002, buprenorphine (BUP) was approved for opiate maintenance and can be prescribed
      by primary care physicians. It is anticipated that many HIV specialists will begin
      prescribing BUP for their HIV+ patients on ARVs with a history of opiate dependence. This
      will continue to increase in importance as a method of treatment for this patient population
      for the following reasons: 1) Multiple federal programs are working to encourage the use of
      BUP in primary care, especially HIV primary care, settings. The goal of these programs is to
      increase opiate treatment slots across the country. 2) Many methadone programs have wait
      lists or regulations (e.g., daily dosing) which may not be possible for some patients. BUP,
      with its flexibility in dosing and ease of use, will increasingly become a first line in the
      treatment of opioid dependence.

      Buprenorphine administration carries the theoretical risk of drug interactions with respect
      to both inhibition or induction of BUP as well as similar effects on medications
      co-administered with BUP. Interactions may lead to under or overdosing of buprenorphine
      and/or antiretroviral agents with resultant adverse clinical consequences.

      Buprenorphine's effects on Kaletra and other ARVs cannot be predicted based on prior
      experience with methadone because BUP metabolism appears to differ from methadone in terms of
      its substrate and effects on cytochrome P450.

      Limited information currently exists regarding interactions between HIV therapeutic agents
      and buprenorphine. Similar to buprenorphine, the protease inhibitors, and NNRTIs are
      metabolized primarily via the CYP3A4 isozyme of the cytochrome P450 system. The extent to
      which methadone levels decrease with induction of cytochrome P450 isoenzymes has been
      correlated clinically with severity of symptoms of withdrawal. Similar studies with
      buprenorphine are not yet available. Interactions between buprenorphine and antiretroviral
      agents may complicate the management of HIV disease when these medications are
      coadministered. In a small sample study, there was no increase in buprenorphine dosing
      required when co-administered with Sustiva. However, in one study with liver microsomes,
      ritonavir inhibited the metabolism of buprenorphine at CYP 3A4, but the clinical significance
      of this inhibition could not be demonstrated. It is well known that in vitro and in vivo
      studies do not fully correlate with one another and empiric pharmacologic interaction studies
      in human subjects are necessary.

      The treatment of opiate addiction is a complicated and labor intensive practice. This study
      will require the use of Kaletra alone in HIV negative opiate dependent patients. This is
      critical to ascertain the reality of both objective data (levels of buprenorphine and
      lopinavir), as well as valid subjective symptoms of opiate withdrawal (symptoms that addicts
      have previously experienced and can more readily communicate).
    

Intervention name(s): Kaletra (lopinavir/ritonavir); buprenorphine; Clinical evaluations/Blood draws
Intervention type(s): Drug; Drug; Other
Intervention description(s): 4 tablets, once a day (800 mg/dose) on Days 2 through 14 of this study; Buprenorphine will be obtained through prescription at the subject's drug treatment program.; Physical examinations, vital sign measurements, 12-lead electrocardiogram (ECG), clinical laboratory evaluations (blood chemistry and blood counts), PK blood draws.
Intervention MeSH terms: Ritonavir; Lopinavir; Buprenorphine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: HIV; Pharmacokinetics; Buprenorphine; Kaletra; HIV Seronegativity