COM4S_M.TTF

Research Focus

Dr. Ambrose’s areas of scientific inquiry primarily involve anti-infective translational science, with the goal of improving patient care through the application of pharmacokinetic-pharmacodynamic (PK-PD) principles. Knowledge gained though the use of non-clinical ( in vitro and animal) PK-PD infection models may be leveraged with human pharmacokinetic data in order to discriminate between potential dosing regimens and thereby increase the probability of positive clinical outcomes while minimizing the potential for drug-related toxicities. We have successfully utilized this approach for regulatory decision-making and as support for Clinical and Laboratory Standards Institute (CLSI, formally NCCLS) susceptibility breakpoint determinations.

Our team’s expertise ranges from the microbiology laboratory, with in vitro PK-PD infection models, to the animal laboratory for PK-PD studies, through the Phase 1 Unit for healthy-volunteer and patient studies, into Phase 2 through 4 clinical trial design, to pharmacokinetic and PK-PD mathematical analyses to support regulatory and commercial efforts. More specifically, our team’s mathematical expertise includes pharmacokinetic and population pharmacokinetic modeling, PK-PD analyses, Monte Carlo simulation, and epidemiological analyses of drug use and antimicrobial resistance.

We are interested in novel PK-PD-based clinical trial design, which serve to better describe the time-course of drug effect. The use of PK-PD-based clinical trial endpoints can have a significant impact on sample size power calculations and thereby hold the promise of reducing the total number of patients required to demonstrate therapeutic efficacy.

Finally, Dr. Ambrose is the author or coauthor of over 50 peer-reviewed scientific publications and approximately 100 scientific abstracts. Finally, Dr. Ambrose has severed as an Editor for four textbooks, most notable the 1st and 2nd Editions of Antimicrobial Pharmacodynamics in Theory and Clinical Practice.

Selected Publications

• Booker BM, Smith PF, Forrest A, Bullock J, Kelchlin P, Bhavnani SM, Ambrose PG. Pharmacokinetic and Pharmacodynamic Characterization of Gatifloxacin Against Salmonella Typhi in an in vitro Infection Model. Antimicrobial Agents and Chemotherapy. 2005;49:1775-1781.
• Ambrose PG, Anon JB, Owen JS, Van Wart S, McPhee ME, Bhavnani SM, Piedmonte M, Jones RN. Use of pharmacodynamic end points in the evaluation of gatifloxacin for the treatment of acute maxillary sinusitis. Clinical Infectious Diseases, 2004;38: 1513-1520.
• Ambrose PG, Bhavnani SM, Cirincione BB, Piedmonte M, Grasela TH. Gatifloxacin and the elderly: Rationale for a potential age-related dose reduction. Journal of Antimicrobial Chemotherapy, 2003;52:435-440.
• Bhavnani SM, Hammel JP, Forest A, Jones RN, Ambrose PG. Relationships between patient- and institutional-specific variables and decreased antimicrobial susceptibility of gram-negative pathogens. Clinical Infectious Diseases, 2003;37:344-350.
• Ambrose PG, Grasela DM, Grasela TH, Passarell J, Mayer HB, Pierce PF. Pharmacodynaics of fluoroquinolones against Streptococcus pneumoniae in patients with community-acquired respiratory tract infections. Antimicrobial Agents and Chemotherapy; 2001;45:2793-2797.
• Dudley MN, Ambrose PG. Pharmacodynamics in the study of drug resistance and establishing in vitro susceptibility breakpoints: ready for prime time. Current Opinion in Microbiology, 2000;3:515-521.