Genetic Predictors of Variability in the Drug-drug Interaction Between Darunavir/Ritonavir and Pravastatin

University of Colorado, Denver32 enrolled

Overview

Pravastatin (Pravachol) is approved by the Food and Drug Administration (FDA) and is used to treat high cholesterol. Darunavir (Prezista) and ritonavir (Norvir) are approved by the Food and Drug Administration (FDA) to treat HIV infection. When darunavir and ritonavir are given with pravastatin, they can increase the blood levels of pravastatin. The degree of this interaction varies from person to person. The way that darunavir and ritonavir interact with pravastatin may be affected by a person's genetic make-up. Genetic factors (or DNA) are those that people are born with and that make each person unique. Genetic differences are the reason why one person's body traits such as height and hair color are different from another person's body traits. Genetic differences can also affect the way a medication works in the body or the way two medications interact in the body. The purpose of this clinical study is to determine if a person's genetic make-up affects the way darunavir and ritonavir interact with pravastatin in the body.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HIV Infections Hyperlipidemia

PravastatinDRUG

Pravastatin 40 mg by mouth daily on days 1-4

DarunavirDRUG

Darunavir 600mg by mouth twice daily on days 12-18

RitonavirDRUG

Ritonavir 100mg by mouth twice daily on days 12-18

PravastatinDRUG

Pravastatin 40 mg by mouth daily on days 15-18

WashoutOTHER

Washout (no medication) on days 5-11.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy, HIV-negative volunteers Exclusion Criteria: * Currently active or chronic cardiovascular, hepatic, renal, pancreatic, gastrointestinal, neurologic, hematologic, psychiatric, metabolic, respiratory, inflammatory, or infectious disease * Chronic pancreatitis * History of rhabdomyolysis * History of statin-associated myopathy * Active malignancy * History of significant skin disease, food allergy, drug allergy, dermatitis, eczema, psoriasis * Pregnancy/breastfeeding * HIV positive and/or AIDS * serum creatinine grade 1 or greater (≥ 1.1 x upper limit of laboratory normal range \[ULN\]); * hemoglobin grade 1 or greater (≤ 10.9 g/dL); * platelet count grade 1 or greater (≤ 124.999 x 109/L); * absolute neutrophil count grade 1 or greater (≤ 1.3 x 109/L); * aspartate aminotransferase (AST) or alanine aminotransferase (ALT) grade 1 or greater (≥ 1.25 x ULN); * total bilirubin grade 1 or greater (≥ 1.1 x ULN) * serum lipase grade 1 or greater (≥ 1.1 x ULN) * serum amylase grade 1 or greater (≥ 1.1 x ULN) * any other laboratory abnormality of grade 2 or above

Outcomes

Primary Outcomes

Relative Change in Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval

AUC of pravastatin when administered with darunavir/ritonavir divided by AUC of pravastatin when administered alone. The AUC was measured over a 24-hour dosing interval.