Pharmacokinetic Interactions Between Buprenorphine and Kaletra (Lopinavir/Ritonavir)

Inclusion Criteria

• Chronic BUP users enrolled in BUP program, receiving BUP for at least 3 months and on a stable BUP dose for at least 3 weeks.
• Acceptable medical history, physical examination, 12 lead electrocardiogram, and clinical laboratory evaluations consistent with BUP maintenance
• Subjects who meet the criteria of opiate dependence, are enrolled in long-term BUP maintenance therapy, and have been on a stable dose of BUP for at least 3 weeks.
• Body weight >60 kg for males and >40 kg for females
• Body Mass Index (BMI) of 18 to 30 kg/m2, inclusive. BMI = weight (kg)/ [height (m)]2.
• Male or females, ages 18 to 65 years.
• Women of childbearing potential (WOCBP) must not be nursing, pregnant and on adequate non-hormonal contraception to avoid pregnancy. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of Study Day 1.

Exclusion Criteria

Sex and Reproductive Status Exceptions

• WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks before and after the study.
• WOCBP using a prohibited contraceptive method (oral, injectable, or implantable hormonal agents)
• Women who are pregnant or breastfeeding
• Women with a positive pregnancy test on enrollment or prior to study drug administration.

Medical History and Concurrent Diseases

• History or current evidence of any significant acute or chronic medical illness that, within the investigator's discretion, would interfere with the conduct or interpretation of the study.
• History of nephrolithiasis
• History of acute or chronic pancreatitis.
• History of uncontrolled chronic medical illness which could adversely affect the subject's adherence to study protocol or affect patient safety in the opinion of the investigator
• Use of any medication thought to significantly alter the metabolism of Kaletra, Buprenorphine or naloxone.
• History of any hemolytic disorders (including drug-induced hemolysis).
• Proven or suspected acute hepatitis at the time of study entry.
• Current or recent (within 3 months) gastrointestinal disease which would interfere with the conduct or interpretation of the study.
• Any major surgery within 4 weeks of enrollment. Minor surgical procedures requiring local anesthesia are exceptions.
• Any gastrointestinal surgery that could impact upon the absorption of study drug.
• Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within 4 weeks of enrollment.
• Blood transfusion within 4 weeks of enrollment.
• Inability to tolerate oral medication.
• Inability to tolerate venipuncture and/or absence of secure venous access.
• Inability to refrain from smoking during in-patient period
• Known or suspected HIV infection (subjects who are found to be positive upon screen for HIV will be excluded).
• Known active drug or alcohol abuse, which in the opinion of the investigator makes study participation to completion unlikely.
• Any other sound medical, psychiatric and/or social reason as determined by the Investigator.

Physical and Laboratory Test Findings

• Evidence of organ dysfunction or any clinically relevant deviations from the norms observed in a buprenorphine treated population in physical examination, vital signs, ECG or clinical laboratory determinations.
• Ingestion of alcohol within 24 hours prior to the dose of study medication
• Positive breathalyzer alcohol test, or positive urine screen for barbiturates, benzodiazepines, amphetamines or opiates other than buprenorphine.
• Positive blood screen for HIV antibody.
• QTc interval >450 msec for males or >470 msec for females.
• Second or third-degree AV block.
• Creatinine clearance(as estimated by method of Cockcroft and Gault) less than 80 mL/min.
• CLcr=0.85(females only)x(140-age)x weight(kg)
• serum creatinine(mg/dL)x 72
• Subjects with bilirubin >2 mg/dL, serum albumin 3