About

Charles Peloquin, Pharm.D., is the Jack C. Massey Endowed Professor and Past Associate Chair of the Department of Pharmacotherapy and Translational Research at the University of Florida College of Pharmacy. Prior to his tenure at UF, he completed a hospital pharmacy residency at Duke University Medical Center, where he also served on the clinical staff. He further completed a fellowship in Infectious Diseases and Pharmacokinetics at the Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, N.Y. For 20 years, Dr. Peloquin was the Director of the Infectious Disease Pharmacokinetics Laboratory at National Jewish Health in Denver, Colorado, where he now serves as a Professor of Pharmacy and Medicine. His laboratory is part of the UF Emerging Pathogens Institute and functions as a national reference center for determining serum concentrations of antimycobacterial, antifungal, anti-HIV, and antibacterial drugs, including beta-lactams and linezolid. His research primarily focuses on therapeutic drug monitoring and clinical trials for patients with advanced mycobacterial diseases. Dr. Peloquin has served as a consultant to the FDA, CDC, and WHO, and has contributed to national guidelines on tuberculosis treatment and the treatment of opportunistic infections in patients living with AIDS. His notable accomplishments include receiving the Roger Jelliffe Individualized Therapy Award in 2024 and the American College of Clinical Pharmacology Lifetime Achievement Award in 2023.

Research topics

• Medicine
• Microbiology
• Biology
• Internal medicine
• Pharmacology
• Pathology
• Immunology
• Intensive care medicine
• Chemistry
• Nuclear medicine
• Anesthesia

Selected publications

• Pharmacokinetics of Dolutegravir in Children with HIV with and without Tuberculosis Coinfection Treated According to World Health Organization Dosing Guidelines

  JAIDS Journal of Acquired Immune Deficiency Syndromes · 2026-03-19

  article

  BACKGROUND: The pharmacokinetics (PK) and safety of dolutegravir in children with HIV (CWH) weighing at least 20 kg with and without tuberculosis (TB) treated according to World Health Organization dosing guidelines was examined. METHODS: CWH on dolutegravir 50 mg once-daily and those with HIV/TB on 50 mg twice-daily with rifampin-based therapy were enrolled. Five to six blood samples were collected within the dosing interval after 4 weeks (period-1) and 7-8 months (period-2) of dolutegravir-based therapy. Dolutegravir concentrations were measured using LCMS/MS and PK parameters calculated by non-compartmental analysis. Geometric mean ratio (GMR) with 95% confidence interval (CI) was used to compare PK parameters on and off TB treatment and between the two groups. RESULTS: Of 25 participants, 52% had TB coinfection. Rifampin coadministration increased dolutegravir clearance by 86%. GMRs (95% CI) of area under the concentration-time curve (AUC0-24h) and trough concentration (Ctrough) of dolutegravir twice-daily with rifampin versus once-daily alone were 1.07 (0.79-1.44) and 1.45 (0.89-2.35), respectively. Comparing HIV/TB versus HIV, dolutegravir AUC0-24h and Ctrough GMRs (respectively) were 1.69 (0.99-2.90) and 2.50 (1.19-5.26) in period-1 and 1.26 (0.85-1.85) and 1.57 (0.53-4.68) in period-2. Two participants with HIV and none with HIV/TB had Ctrough <0.32mg/L. Overall, 92% of participants with HIV/TB and 82% with HIV achieved viral load <400 copies/mL at 6 months of dolutegravir-based therapy, with no dolutegravir discontinuations. CONCLUSIONS: Twice-daily dolutegravir with rifampin was associated with higher trough concentrations in children with HIV/TB than in controls. Standard dose of dolutegravir with rifampin needs to be investigated.

  PublisherDOI

• Identifying optimal combination regimens for therapy of Mycobacterium tuberculosis with an algorithmic approach: prospective predictions and validations

  PLoS ONE · 2026-02-10

  articleOpen access

  BACKGROUND: Mycobacterium tuberculosis resistance to standard-of-care agents is increasing. It is imperative to identify new combinations that increase the rate and depth of bacterial kill, shorten therapy and also suppress resistance. There has been little prior effort to identify combination regimens that employ new or repurposed drugs in a rational way. METHODS AND FINDINGS: Our group developed a pathway to combine agents to achieve this end. This pathway starts with standard baseline evaluations (e.g., MIC), leverages information from in vitro assessments (hollow fiber infection model), then analyzes 2-agent combinations in a 96 well quantitative culture checkerboard format (Greco URSA model with simulation). Finally, development of a high dimensional mathematical model allowed evaluation of 2- and 3-drug regimens in multiple metabolic states to draw inferences regarding combination therapies. We prospectively evaluated these regimens in animal models. We showed that a prospectively chosen regimen of pretomanid, moxifloxacin plus bedaquiline performed as predicted. In the BALB/c murine model, this regimen produced sterilization in a cohort that was held for 12 weeks after therapy cessation, as it did in the C3HeB/FeJ ("Kramnik") murine model. Finally, this and other regimens were evaluated in a cynomolgus macaque model. The decrement of the 18F-deoxyglucose signal in Positron emission tomography (PET)- computed tomography (CT) evaluations was best with this regimen. Other endpoints such as necropsy score and colony counts in lung and lymph nodes also demonstrated that this regimen behaved as predicted from our pathway/algorithm. CONCLUSIONS: We conclude that this provides a way forward for the future to identify the most promising regimens to shorten therapy for tuberculosis and suppress emergence of resistance.

  PublisherDOI

• Population pharmacokinetics and safety of continuous oxacillin in preterm and term neonates and infants

  Antimicrobial Agents and Chemotherapy · 2026-04-20

  articleOpen access

  T>MIC) 100% of dosing interval is a desired pharmacodynamic (PD) target in immunocompromised/septic patients. Our objective was to characterize oxacillin pharmacokinetics (PK) and PD in young infants. We conducted a prospective PK/PD study in infants ≤90 days. We divided four cohorts per gestational (GA <32/≥32 weeks) and postnatal age (PNA <14/≥14 days). Patients received 25 mg/kg loading doses followed by continuous infusions of 120 (<32 weeks/<14 days) or 160 mg/kg/day. Population PK parameters were estimated using NONMEM. Dosing regimens were evaluated using Monte Carlo simulations to estimate the probability of PD target attainment. Outcomes were collected. We enrolled 22 infants, median (IQR) GA 38 weeks (30-39) and PNA 32 days (12-46). PNA and weight were covariates for oxacillin clearance. Unbound steady-state oxacillin concentrations remained >MIC 0.5 throughout the dosing interval for >90% of modeled patients for all age groups on 160 mg/kg/day continuous infusions. Infants with PNA ≤28 days met PD targets at MIC 1; <90% of all modeled patients on continuous infusion met PD targets at MIC 2. Modeled infants receiving 200 mg/kg/day oxacillin divided q4h/q6h failed to meet PD targets up to MIC 2. All patients survived to discharge. A few serious adverse events were noted. 160 mg/kg/day continuous oxacillin was well tolerated and achieved PD targets for MIC ≤0.5 across all age groups. Modeled intermittent dosing ≤200 mg/kg/day divided q4h/q6h, 8 times the Food and Drug Administration-labeled dose of 25 mg/kg daily, failed to achieve PD targets. The FDA-recommended oxacillin dose is inadequate and may help explain high mortality.

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• 568. Comparative Analysis of Cefazolin Target Attainment in Methicillin-Susceptible Staphylococcus aureus (MSSA) Isolates With and Without the Cefazolin Inoculum Effect (CzIE)

  Open Forum Infectious Diseases · 2026-01-01

  articleOpen access

  Abstract Background Clinical failures with cefazolin have been linked to the CzIE where increased bacterial inoculum leads to elevated cefazolin minimum inhibitory concentrations (MICs) against MSSA. The role of therapeutic drug monitoring (TDM) in optimizing cefazolin dosing in the context of the CzIE remains unclear. This study aimed to determine the prevalence of the CzIE and compare cefazolin pharmacokinetic/pharmacodynamic (PK/PD) target attainment in MSSA isolates with and without the CzIE. Methods A single-center, retrospective review included adults (≥18 years) with MSSA bacteremia admitted between Jun 2021–Dec 2023 who received cefazolin and had steady-state serum cefazolin concentrations. CzIE was defined as a cefazolin MIC ≥16 µg/mL at high inoculum (10⁷ CFU/mL) and ≤8 µg/mL at standard inoculum (10⁵ CFU/mL). Total cefazolin concentrations were adjusted for 80% protein binding. PK/PD targets were 100%fT≥MIC and 100%fT≥4×MIC (100% free drug time above MIC or 4x MIC, respectively). Results Among 51 patients included in the analysis, median age was 61 years (IQR, 39.5–70.5). Common bacteremia sources included endocarditis (n=11, 21.6%), musculoskeletal (n=11, 21.6%), and pneumonia (n=9, 17.6%). Nine isolates (17.6%) exhibited the CzIE and 32 (62.7%) were blaZ-positive. Median cefazolin trough was 5.9 µg/mL (IQR, 3.2–11.6) in CzIE infected vs. 4.2 µg/mL (IQR, 2.5–10.4) in patients infected with a non-CzIE isolate. In CzIE isolates, modal MICs were 1 µg/mL at standard inoculum and 16 µg/mL at high inoculum; in non-CzIE, both were 0.5 µg/mL. In the CzIE group at standard inoculum, 100% (n=9) achieved 100%fT≥MIC and 66.7% (n=6) achieved 100%fT≥4×MIC; at high inoculum, 11.1% (n=1) achieved 100%fT≥MIC and none achieved 100%fT≥4×MIC. In the non-CzIE group at standard inoculum, 88.1% (n=37) achieved 100%fT≥MIC and 73.8% (n=31) achieved 100%fT≥4×MIC; at high inoculum 88.1% (n=37) achieved 100%fT≥MIC and 61.9% (n=26) achieved 100%fT≥4×MIC. Conclusion Cefazolin PK/PD target attainment was markedly reduced in patients with CzIE isolates at high inoculum. These findings underscore the potential utility of TDM in detecting suboptimal cefazolin exposure and the need to consider alternative dosing strategies in this setting. Disclosures Cesar A. Arias, MD/PhD, UptoDate: Royalties

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• Exposure to the Four First-Line Anti-Tuberculosis Drugs and Treatment Outcomes: A Target Trial Emulation Study in Ghana

  Research Square · 2026-04-10

  preprintOpen access
  PublisherOA PDFDOI

• Pharmacokinetic and pharmacogenomic predictors of hepatotoxicity in the HIRIF trial for drug-susceptible tuberculosis

  Clinical Infectious Diseases · 2026-03-04

  articleOpen access

  BACKGROUND: Hepatotoxicity is frequent in the standard-of-care regimen for drug-susceptible tuberculosis, yet the association of each companion drug with hepatotoxicity has not been fully characterized. We examined the association between hepatotoxicity and the pharmacokinetics of rifampin and its companion drugs in standard therapy, as well as N-acetyltransferase 2 (NAT2) genotype. METHODS: We evaluated HIRIF trial participants who were randomized to receive rifampin 10, 15, or 20 mg/kg/day during the intensive phase of tuberculosis treatment. We fitted Cox proportional hazards models to identify risk factors for grade 2 or higher (grade 2+) alanine transaminase (ALT) or aspartate transaminase (AST) elevation, and considered pharmacokinetic exposure of each antituberculosis drug and NAT2 genotype as potential covariates. RESULTS: Among 168 participants with pharmacokinetic data, neither rifampin dose nor exposure were associated with the risk of grade 2+ ALT or AST elevation. Higher pyrazinamide exposure (hazard ratio [HR] 1.85 for every 50 mg*h/L AUC0-6h increase), higher isoniazid exposure (HR 1.40 for every 5 mg*h/L AUC0-6h increase), and among a subset with known NAT2 genotype, slow NAT2 acetylator status (HR 9.32 relative to fast, n=90) were associated with grade 2+ ALT or AST elevation in univariable analysis. In multivariable analysis, only pyrazinamide exposure was associated with hepatotoxicity. CONCLUSIONS: While higher pyrazinamide and isoniazid exposures and slow NAT2 acetylator status were each associated with increased hepatotoxicity, only pyrazinamide exposure was associated when considering pharmacokinetic variables together. Rifampin exposure was not associated with hepatotoxicity, supporting further evaluation of doses up to 20 mg/kg/day in a larger trial.

  PublisherDOI

• Addition of Clofazimine Enhances the Activity of Standard Treatment Regimen in a Mouse Model of Tuberculous Meningitis

  The Journal of Infectious Diseases · 2026-02-21

  articleOpen access

  Tuberculous meningitis causes substantial mortality due to limited penetration of antibiotics to the central nervous system and excessive neuroinflammation. This study evaluated clofazimine as an adjunct to the standard first-line tuberculosis regimen, in a mouse model. Mice were infected intracerebrally with Mycobacterium tuberculosis and treated for six weeks. Addition of clofazimine markedly reduced the brain bacterial burden, achieving measurable brain tissue concentrations despite minimal cerebrospinal fluid penetration, as well as attenuated brain tissue inflammation. These findings indicate that clofazimine enhances bactericidal activity of the standard regimen and mitigate neuroinflammation, supporting further investigation and clinical evaluation for tuberculous meningitis.

  PublisherDOI

• P-1244. PK/PD Target Attainment of Beta-lactams in Patients With Versus Without Obesity

  Open Forum Infectious Diseases · 2026-01-01

  articleOpen access

  Abstract Background Previous studies have shown that patients with obesity are at risk for subtherapeutic beta-lactam concentrations, owing to the pharmacokinetic (PK) changes in factors such as volume of distribution and clearance. Beta-lactam therapeutic drug monitoring (TDM) has been utilized as a strategy to reduce PK variability and individualize dosing regimens, although data exploring the use of TDM in this population are limited. This study sought to evaluate the role of TDM in patients with obesity and its impact on pharmacokinetic/pharmacodynamic (PK/PD) target attainment of beta-lactams. Methods This single-center, retrospective, matched cohort study included adult patients with obesity (OB) and patients without (non-OB) who had routine TDM performed for cefepime (FEP), piperacillin-tazobactam (PTZ), or meropenem (MEM). Underweight patients were excluded. Patients were matched by drug, ICU status, renal function, and early (≤ 72 hours) or late TDM ( &amp;gt; 72 hours). The primary outcome compared PK/PD target attainment in OB vs non-OB. This study assessed two PK/PD targets (100% fT≥ MIC and 100% fT≥ 4xMIC). Secondary outcomes included treatment failure, length of stay, in-hospital mortality, adverse events, and 30-day readmission. Results Of 199 matched pairs of patients, 298 (75%) patients received FEP, 48 (12%) received PTZ, and 52 (13%) received MEM. There was no difference in attainment of 100% fT≥ MIC between OB vs non-OB at 84% (n=168) and 85% (n=170), respectively. Target attainments were similar, yet much lower for 100% fT≥ 4xMIC in OB vs non-OB at 53% (n=106) and 54% (n=108) respectively. OB and non-OB receiving PTZ had the lowest overall rates of attainment of 100% fT≥ MIC (69%) and 100% fT≥ 4xMIC (29%). More OB experienced any adverse effect compared to non-OB at 48 (24%) and 30 (15%), respectively (p = 0.02). Specifically, rates of nephrotoxicity were greater in OB vs non-OB (15% vs. 6%, p&amp;lt; 0.01). There were no differences in any other secondary outcomes. Conclusion PK/PD target attainment was comparable between OB and non-OB in this study, but lowest with PTZ, highlighting the need for targeted TDM in these patients. OB experienced significantly higher rates of adverse effects, including nephrotoxicity, emphasizing the importance of TDM in improving patient safety. Disclosures Venugopalan Veena, PharmD, Merck: Grant/Research Support Kathryn DeSear, PharmD, Abbvie: Advisor/Consultant|Biomerieux: Advisor/Consultant|Cormedix: Speaking|GSK: Advisor/Consultant|Shionogi: Speaking

  PublisherDOI

• Population pharmacokinetics of pyrazinamide and ethambutol in children with tuberculosis with or without HIV

  Antimicrobial Agents and Chemotherapy · 2026-03-02

  articleOpen access

  ABSTRACT Tuberculosis (TB) is a major cause of morbidity and mortality in children globally. This study developed models to describe population pharmacokinetics (PK) of pyrazinamide (PZA) and ethambutol (EMB) in children with TB with or without human immunodeficiency virus (HIV) coinfection. Ghanaian children with TB with or without HIV coinfection receiving first-line antituberculosis therapy for at least 4 weeks had blood samples collected at time 0 (pre-dose), 1-, 2-, 4-, 8-, and 12-h post-dose. PZA and EMB concentrations were quantified using liquid chromatography tandem mass spectrometry. Nonlinear mixed-effects models were applied to describe the population PK using Monolix2024R1. Maximum concentrations ( C max ) and 24-h area under the time concentration curve (AUC 0–24 ) were compared to published values in adults. A total of 85 children (41 TB, 44 TB/HIV) were included. The median (range) age was 5 years (0.3–14.5), and 61.2% were male. Median (range) doses for PZA and EMB were 31.6 (21.4–49.7) and 21.4 mg/kg (14.3–34.2), respectively. PZA was best described using a one-compartment model and EMB by a two-compartment model. Allometric scaling improved both model fits. Children with TB/HIV coinfection had approximately 18.5% faster PZA clearance and 25% faster EMB clearance. Optimized dosing to achieve adult-equivalent exposures required higher-than-currently recommended doses, particularly among children in the lowest weight bands and those with HIV. The population PK of PZA and EMB was well described by the final models, but the higher-than-currently recommended doses needed to achieve adult-equivalent exposures raise concerns regarding risks for drug-associated toxicities and will require further evaluation.

  PublisherDOI

• 333. Comparative Efficacy of Rifamycin-containing Regimens in a Murine Model of Tuberculous Meningitis

  Open Forum Infectious Diseases · 2026-01-01

  articleOpen access

  Abstract Background Tuberculous meningitis (TB meningitis), the most severe form of tuberculosis (TB), is associated with high mortality and neurological sequelae. Standard therapy includes rifampin, a key drug for pulmonary TB; however, its efficacy in TB meningitis is hampered by poor blood-brain barrier penetration, often resulting in subtherapeutic concentrations. While alternative rifamycins like rifapentine and rifabutin exhibit distinct pharmacokinetic advantages, including reduced cytochrome P450 induction, and have been evaluated for pulmonary TB, their utility in TB meningitis remains unexplored.Figure 1.Evaluation of rifamycin-containing regimens in the mouse model of TB meningitis.(A) Mice were infected intraventricularly via Burr hole using a syringe and stereotaxic instrument, treatment were initiated two weeks after (designated as day 0) and continued for six weeks. Mice were randomly allocated to receive multi-drug regimens HRZ, HRZMx, HPZMx, or HRbZ. Isoniazid (10 mg/kg/day), pyrazinamide (150 mg/kg/day), rifampin (10 mg/kg/day), rifapentine (20 mg/kg/day), rifabutin (10 mg/kg/day), and moxifloxacin (100 mg/kg/day divided twice daily) were administered via oral gavage. Mouse dosing was utilized to match the standard human equipotent dosing: isoniazid (10 mg/kg/day), pyrazinamide (25 mg/kg/day), rifampin (10 mg/kg/day), rifapentine (1200 mg), rifabutin (300 mg), and moxifloxacin (400 mg). All regimens received adjunctive dexamethasone via intraperitoneal injection. After completions of antibiotic treatment, mice were sacrificed, tissue were homogenized and colony forming unit (CFU) were enumerated ex vivo. (B-C) Bacterial burden in brain [per gram of brain tissue (log10) from whole brain] at two and six weeks of treatment (animal numbers, n = 11/RHZ, 10/HRZMx, 10/HPZMx, and 10/HRbZ). (D) Bacteria disseminate to the lungs after the brain infection. Therefore, bactericidal activities of the antibiotic rifamycin-containing regimens in brain and lung tissues of the same animal, two and six weeks after treatment initiation, were assessed. (E) Bactericidal activity in brain and lung from the same animals. Data are shown as the reduction in whole brain (solid bar) and lung (checkered bar) organ CFU [per gram of lung tissue (log10) from whole lungs] two weeks after treatment initiation. Animal studies were approved by the Johns Hopkins Animal Care and Use Committee. Data are presented as mean ± SD on a logarithmic scale. Each dot represents a mouse.Figure 2.Antibiotic tissue penetration of rifamycins after two weeks of treatment.(A) Brain, CSF and plasma rifampin, rifapentine, and rifabutin levels measured by mass spectrometry in M. tuberculosis-infected mice with TB meningitis after two weeks of treatment. (B) Tissue-to-plasma ratios from brain and CSF tissues for each rifamycin. Rifampin data from six animals; n = 6 brain samples, n = 6 CSF samples, n = 6 plasma samples. Rifapentine data from six animals; n = 6 brain samples, n = 4 CSF samples, n = 6 plasma samples. And Rifabutin data from six animals; n = 6 brain samples, n = 4 CSF samples, n = 6 plasma samples. Data are represented as median ± interquartile range. Each dot represents a mouse. Methods We performed preclinical studies in a mouse model of TB meningitis to compare the efficacy and CNS penetration of three rifamycin-containing regimens: standard HRZ (isoniazid, rifampin, pyrazinamide), HPZMx (isoniazid, rifapentine, pyrazinamide, moxifloxacin – recently approved as a 4-month regimen for pulmonary TB), and HRbZ (isoniazid, rifabutin, pyrazinamide). All mice received adjunctive dexamethasone. Mice were intracranially inoculated with M. tuberculosis and treatment was started two weeks after incubation. The bacterial burden was quantified after two and six weeks of treatment (Fig. 1A). Drug concentrations in plasma, brain, and cerebrospinal fluid (CSF) were measured by mass spectrometry. Brain magnetic resonance imaging (MRI) with gadolinium-enhanced contrast imaging was performed in live animals and postmortem cytokine levels in CSF were used to assess inflammation and tissue damage.Figure 3.MRI assessment of brain involvement in a mouse model of tuberculous meningitis under different treatment regimens.(A) Representative axial T1-weighted MR images acquired pre-contrast (left column) and post-contrast (middle column) with corresponding delta maps (right column) showing gadolinium contrast enhancement indicative of brain involvement. Images are shown for five groups: Sham (PBS-injected, without infection), untreated (infected, no treatment), and three treatment groups receiving rifamycin-containing regimens-HRZ (isoniazid, rifampin, pyrazinamide), HPZMx (isoniazid, rifapentine, pyrazinamide, moxifloxacin), and HRbZ (isoniazid, rifabutin, pyrazinamide). (B) Quantitative analysis of mean signal intensity before and after contrast administration across groups, showing increased enhancement in untreated mice compared to treated and sham controls. (C) Delta of intensity (post-contrast minus pre-contrast) for each group, demonstrating significant brain involvement in untreated mice and reduced enhancement in all treatment groups. Data are presented as median ± interquartile range. Each dot represents a mouse. Results Both rifapentine- and rifabutin-containing regimens demonstrated significant bactericidal activity in the brain, similar to the standard HRZ regimen (Fig. 1B-C). However, activity of all three regimens was higher in the lungs compared to the brain (Fig. 1D-E). All three rifamycins achieved higher concentrations in brain tissue than in CSF (Fig. 2). MRI studies demonstrated substantially reduced tissue damage and inflammation within all regimens (Fig. 3). All regimens also reduced CSF inflammatory cytokine levels. Conclusion Rifapentine- and rifabutin-containing regimens demonstrated comparable bactericidal activity to standard HRZ in the brain. These results support further clinical evaluation of rifapentine and rifabutin for TB meningitis. Disclosures All Authors: No reported disclosures

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Recent grants

• Administrative Core

  NIH · $24.0M · 2016–2022

• NIH Grant R01AI037845

  NIH · $1.0M · 2000

Frequent coauthors

• Andrew Vernon

  Centers for Disease Control and Prevention

  177 shared

• William J. Burman

  Public Health Institute

  160 shared

• Marc Weiner

  153 shared

• Awal Khan

  Centers for Disease Control and Prevention

  130 shared

• Stephen E. Weis

  Nuffield Health

  128 shared

• Debra Benator

  Washington DC VA Medical Center

  88 shared

• Charles L. Daley

  University of Colorado Anschutz Medical Campus

  86 shared

• Zhen Zhao

  72 shared

Labs

• Infectious Disease Pharmacokinetics LabPI

Education

• Other, Hospital Pharmacy

  Duke University Medical Center

• Other, Infectious Diseases and Pharmacokinetics

  Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital

• Other, Infectious Disease Pharmacokinetics

  Infectious Disease Pharmacokinetics Laboratory (IDPL)

Awards & honors

• Roger Jelliffe Individualized Therapy Award 2024
• American College of Clinical Pharmacology Lifetime Achieveme…