# Clinical Pharmacology of Malaria Control and Elimination: Pharmacodynamics ofArtemisinin-based Combination Agents and their Barriers to Drug Resistance

> **NIH NIH K23** · JOHNS HOPKINS UNIVERSITY · 2022 · $190,080

## Abstract

Project Summary/Abstract
Background. The proposed mentored research program is an investigation of chemotherapeutics for malaria
elimination led by Dr. Matthew Ippolito under the mentorship of Dr. Theresa Shapiro, an expert in antiparasitic
pharmacology, and others. The project will join clinical pharmacology analytics with molecular and genetic
approaches to establish the pharmacokinetics (PK, drug exposure) and pharmacodynamics (PD, drug effect)
of first-line antimalarial agents for gametocyte clearance and protection against reinfection, and characterize
their relative barriers to drug resistance. Dr. Ippolito will acquire expertise in advanced PK/PD methods and
clinical trial conduct. At the end of the award period, he will be prepared to pursue a career as an independent
investigator with a focus on field-based clinical pharmacology studies of antimalarial drugs both extant and
novel.
Candidate. Dr. Ippolito is a board-certified internist, infectious disease specialist, and clinical pharmacologist at
the Johns Hopkins University School of Medicine, and PhD candidate in the Johns Hopkins University
Graduate Training Program in Clinical Investigation with a background in malaria-related research.
Research. The proposed research will leverage existing and forthcoming clinical trial specimens from study
participants treated for uncomplicated malaria with one of two antimalarial drug combinations, artemether-
lumefantrine or dihydroartemisinin-piperaquine. Specimens will be processed to generate PK data (drug
concentration) and PD data (parasitological outcomes, drug resistance genotypes). PK and PD variables will
be analyzed using compartmental and nonlinear mixed effects models.
Environment and Funding. The research activities will be carried out at Johns Hopkins University and
collaborators' institutions. The antiparasitic laboratories of the primary mentor, Theresa Shapiro, MD, PhD—
former director of the Johns Hopkins Division of Clinical Pharmacology and previous head of its Clinical
Pharmacology Analytical Laboratory—contain the requisite instrumentation for liquid chromatography-mass
spectrometry PK analyses; and the laboratories of the Johns Hopkins Malaria Research Institute and its
partners have state-of-the-art instruments for molecular diagnostics and genetic sequencing of malaria
parasites.
Relevance to Public Health. Malaria remains a major public health issue, with nearly a half-million deaths
each year arising from over 200 million infections. Absent a sufficiently effective vaccine, antimalarial drugs
remain a vital component of malaria control programs. Their incompletely characterized PK/PD profiles and
unknown barriers to resistance translate to opportunities for further research to inform drug optimization. The
proposed training plan and analytic approaches also have potential applications to new antimalarial agents as
they emerge from the drug development pipeline.

## Key facts

- **NIH application ID:** 10333361
- **Project number:** 5K23AI139343-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Matthew Michael Ippolito
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $190,080
- **Award type:** 5
- **Project period:** 2020-02-13 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10333361

## Citation

> US National Institutes of Health, RePORTER application 10333361, Clinical Pharmacology of Malaria Control and Elimination: Pharmacodynamics ofArtemisinin-based Combination Agents and their Barriers to Drug Resistance (5K23AI139343-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10333361. Licensed CC0.

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