University of Colorado
Skaggs School of Pharmacy and Pharmaceutical Sciences
Department of Pharmaceutical Sciences
Mail Stop C238, V20-2108
12850 E. Montview Blvd.
Aurora, CO 80045
Pharmacy and Pharmaceutical Sciences Building (V20)
Second Floor, 2460A
Training and Education:
Post-doctoral Fellowship: Pharmaceutical Chemistry, University of California, San Francisco
PhD: Medicinal Chemistry, University of Washington
MS: Microbiology, Idaho State University
BS: Biological Sciences, Walla Walla University
Each year thousands of sick and premature infants are treated with a variety of medications, despite the fact that many of these drugs have never been tested for safety and efficacy in this fragile patient population. The primary goal of the Lampe lab is to understand how drug metabolism modulates efficacy and toxicity in the developing infant in order to make medications safer for these vulnerable patients.
Drug metabolism is a major determinant of the pharmacokinetic and toxicological profile of many drugs, however little is known about how the infant liver metabolizes drugs, particularly those involved in treating HIV infection.
In adults, the cytochrome P450 enzyme CYP3A4 metabolizes >50% of currently marketed drugs. In contrast, CYP3A7 is the predominant P450 enzyme in the developing infant. Although they share a high degree of structural identity (87%), our group and others have demonstrated that CYP3A7 metabolizes many drugs, including HIV inhibitors, differently than CYP3A4. These differences in metabolism can alter the pharmacokinetic and safety parameters of drugs used in infants, either leading to reduced efficacy (due to increased clearance) or increased toxicity (due to reduced clearance).
Because of this, there is a critical need to understand both how and why CYP3A7 metabolizes drugs differently than CYP3A4, both for drugs in current use and for the future development of drugs specifically targeted to infants. Our current focus is to determine the functional consequences and mechanistic basis of the differences in HIV drug metabolism and inhibition between CYP3A7 and CYP3A4, using both in vitro and hepatocyte cell culture models of drug metabolism. The results obtained from this work will improve our understanding of CYP3A7 mediated drug metabolism and inhibition, providing important knowledge that can be used to improve outcomes and reduce suffering in sick and premature infants.
A complete list of published work can be found in My NCBI Bibliography.