Research Prospectus

Antiviral Clinical Pharmacology Unit Department of Pharmacy Practice School of Pharmacy and Pharmaceutical Sciences University at Buffalo

Clinical Research Recently Presented Research Posters

The Antiviral Clinical Pharmacology Unit (ACPU) was established in 1993 by the Laboratory for Antiviral Research and the Department of Pharmacy Practice at The State University of New York at Buffalo School of Pharmacy and Pharmaceutical Sciences in collaboration with the Immunodeficiency Services Clinic at the Erie County Medical Center.  Areas active research in the ACPU focus on the pharmacology and pharmacokinetics of antiretroviral medications, including drug-drug and drug-food interactions, pharmacokinetics in special populations (i.e. premenopausal women, patients with achlorhydria, and patients with acute opportunistic infections), and medication adherence.  The unit had also been involved in studying antiretroviral usage patterns and post-marketing safety and surrogate marker responses to antiretroviral medications.  Since its inception, the ACPU has conducted approximately 12 independently-funded protocols and 7 pharmacokinetic protocols for various pharmaceutical companies (Glaxo-Wellcome, Pharmacia & Upjohn, Janssen Pharmaceutica, and Roche), working closely with their respective monitoring agencies (PPD, Parexcel, etc.) The staff of the ACPU has expertise in all aspects of clinical research, ranging from protocol development and execution to statistical and pharmacokinetic analyses.  

The ACPU is located within the Immunodeficiency Services (IS) Clinic at ECMC and collaborates with the Clinic for patient recruitment, monitoring, and follow-up.  The ACPU is equipped with two patient rooms (each room contains a reclining chair, a TV/VCR, a sink) which open onto a "nursing station" area where supervisory personnel have office space for completion of case-report forms.  A two-person laboratory area with a centrifuge, two glass shields, a freezer, a dry ice storage container, and a sink is located behind a partition behind the "nursing station" area.  The entire ACPU is conveniently located off the waiting room of the IS clinic.  This location is ideal, maintaining close proximity to the IS clinic to facilitate medical supervision, yet study procedures are separated from general clinic activities.  The onsite hospital laboratory is responsive to requests for "stat" lab results.  ACPU personnel include a full-time clinical pharmacist/study coordinator and a full-time nurse.  An additional full-time "patient care" pharmacist routinely monitors patients' therapy, with extensive clinical activities including adherence counseling for patients, consultation for medical providers regarding drug-drug interactions, adverse effects management, and recommendations for "salvage" therapy.  This pharmacist serves as an ideal source for potential study referral.  The ACPU has developed a computerized database to maintain information about antiretroviral medications and surrogate marker responses in all clinic patients. The database has a multitude of purposes, ranging from patient care, to study recruitment, to analysis of post-marketing antiretroviral safety and clinical outcomes. 

A new General Research Center has been opened which provides the ACPU with a nine-bed facility.  This facility has been operational since August of 2000 and is ideally suited to larger studies of healthy volunteers and studies requiring overnight confinement.

ACPU Protocol History:

Industry-Sponsored

"A phase I pharmacokinetic study comparing 3 dosing regimens of oral ganciclovir and IV ganciclovir in HIV+ subjects with varying degrees on renal dysfunction.", Roche, 1997.

"Pharmacokinetics study of IV itraconazole followed by oral dosing at 200 mg twice daily in patients with advanced HIV infection", Janssen Pharmaceutica Inc., 1996.

"Delavirdine-ritonavir interaction study in HIV+ patients", Pharmacia & Upjohn, Inc., 1997

"Delavirdine mesylate: effect of cytokines on DLV pharmacokinetics", Pharmacia & Upjohn, Inc., 1996

"Delavirdine mesylate: effect of gltuamic acid on DLV pharmacokinetics", Pharmacia & Upjohn, Inc., 1996

"Delavirdine mesylate: multiple dose pharmacokinetics on DLV in hypochlorhydria and euchlorhydria", Pharmacia & Upjohn, Inc, 1995

Subsequent Publications

Shelton MJ,Cloen D, Becker M, Hsyu,Wilton JH, Hewitt RG. Evaluation of the Pharmacokinetic (PK) Interaction Between Phenytoin (Phen) and Nelfinavir (NFV) in Healthy Volunteers at Steady State.  Presented at the 40^th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Toronto, Canada, September 2000.

Morse GD, Shelton MJ, Hewitt RG, et al.  Ritonavir pharmacokinetics during combination therapy with delavirdine.  Presented at the Fifth Conference on Retroviruses and Opportunistic Infections.  Chicago, IL, February 1-6, 1998.

Shelton MJ, Adams JM, Hewitt RG, Morse GD.  Previous Infection with Helicobacter pylori Is the Primary Determinant of Spontaneous Gastric hypoacidity in Human Immunodeficiency Virus-Infected Outpatients. Clinical Infect Dis 1998;27:739-45. [PubMed]

Shelton M, Adams J, Hewitt R, et al.  Reduced delavirdine exposure in HIV+ subjects with gastric hypoacidity. Presented at the 35^th Interscience Conf erence on Antimicrobial Agents and Chemotherapy (ICAAC), San Francisco, CA, September 17-20, 1995.

Shelton MJ, Adams JM, Hewitt RG, et al.  Effects of spontaneous gastric hypoacidity on the pharmacokinetics of zidovudine and didanosine.  Pharmacotherapy. 1997;17:438-44. [PubMed]

Morse G, Adams J, Shelton M, et al.  Gastric acidification increases delavirdine (DLV) exposure in HIV+ subjects with gastric hypoacidity (GH).  Presented at the 97^th Annual meeting of the American Society for Clinical Pharmacology and Therapeutics, March 20 - 22, 1996.

Cordaro JA, Morse GD, Bartos L, Gugino LJ, Maliszewski M, Colomaio R, Shelton M, et al.  Zidovudine pharmacokinetics in HIV-positive women during different phases of the menstrual cycle.  Pharmacotherapy. 1993;13:369-77. [PubMed]

Independently-Funded Protocols:

Shelton MJ, Wynn H, Hewitt RG, DeFrancesco R. Effects of Grapefruit Juice on Pharmacokinetic Exposure to Indinavir in HIV-Positive Subjects.  J Clin Pharmacol.  2001 Apr.41(4):435-442. [PubMed]

Shelton MJ, Mei H, Hewitt RG, DeFrancesco R.  If Taken 1 Hour Before Indinavir, Didanosine Does Not Affect IDV Exposure, Despite Persistent Buffering Effects.  Antimicrob Agents Chemother.  2001;45:298-300. [PubMed]

Shelton MJ, Akbari B, Hewitt RG, Adams JM, Morse GD.  Eradication of Helicobacter pylori is associated with increased exposure to delavirdine in hypochlorhydric HIV-positive patients. J Acquir Immune Defic Syndr 2000:24:79-82.

Adams JA, Frost C, Shelton M, et al.  Indinavir pharmacokinetics and menstrual cycle physiology.  Presented at Presented at the Fifth Conference on Retroviruses and Opportunistic Infections.  Chicago, IL, February 1-6, 1998.

Shelton MJ, Adams JA, Hewitt RG, et al.  Impact of HIV on gastric pH and H. pylori serology in persons of color. Presented at the Spring Practice and Research Forum of the American College of Clinical Pharmacists, Palm Springs, CA, April 5-8, 1998.

Adams JM, Shelton MJ, Hewitt RG, et al.  Relationships between didanosine exposure and surrogate marker response in HIV-infected outpatients.  Antimicrob Agent Chemother 1998;42:821-6. [PubMed]

Adams JA, Shelton MJ, Hewitt RG, et al.  Zalcitabine Population Pharmacokinetics: application of radioimmunoassay. Antimicrob Agents Chemother. 1998;42:409-13. [PubMed]

Huang E, Hewitt RG, Shelton MJ, et al.  Comparison of measured and estimated creatinine clearance in patients with advanced HIV disease.  Pharmacotherapy.  1996;16:222-9. [PubMed]

Clinical/Post-marketing/Adherence:

Esch LD, Hardy H, Wynn HE, Shelton MJ, Hewitt RG, Morse GD.  Intensive adherence interventions improve virologic response to antiretroviral therapy (ART) in treatment naive patients.  Accepted for presentation at the Eighth Conference on Retroviruses and Opportunistic Infections.  Chicago, IL, February 4-8, 2001.

Esch LD, Hardy H, Wynn H, Shelton MJ.  Discrepancy between patient-reported and pharmacist-assessed adherence to antiretroviral therapy in patients with human immunodeficiency virus (HIV). Presented at the ACCP Annual Meeting, Los Angeles, CA, November 2000.

Shelton MJ, Ritterman Y, Esch LD, Ksiazek S, Rozek S. Provider Identified Adverse Drug Reactions in HIV Patients: Prevalence and Characterization.  Accepted for presentation at the ACCP Annual Meeting, Los Angeles, CA, November 2000.

Shelton MJ, Esch LD, Hewitt RG, et al.  The Impact of Patient-Reported Adherence with Antiretroviral Therapy on Virologic Response.  Submitted to the 38^th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), San Diego, CA.

Hewitt RG, Shelton MJ, Esch LD.  Gemfibrozil effectively lowers protease-inhibitor-associated hypertriglyceridemia in HIV-1 positive patients.  AIDS.  1999;13:868-9

Shelton MJ, et al.  Computerization facilitates clinical decision making by integrating medication profiles, adherence, and surrogate markers in real time.  Accepted for presentation at the 12^th World AIDS Conference, Geneva, Switzerland, June 28 - July 3, 1998.

Esch L, Hewitt RG, Shelton MJ, et al. HIV Pharmaceutical care specialist (PCS): an alternative model for patients with HIV. Accepted for presentation at the 12^th World AIDS Conference, Geneva, Switzerland, June 28 - July 3, 1998.

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