Impact of Formulation on Ciprofloxacin Oral Absorption
Information source: University of Maryland
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy
Intervention: ciprofloxacin (Drug)
Phase: Phase 1
Status: Not yet recruiting
Sponsored by: University of Maryland Overall contact:
James Polli, Phone: 410-706-8292, Email: jpolli@rx.umaryland.edu
Summary
Dogs and humans exhibit differences in gastrointestinal physiology. The development of
pharmaceuticals for both humans and dogs typically depends upon pharmacokinetic studies in
the other species. Product design and quality attributes for dogs (and for humans)generally
conduct such extrapolations in a simplistic fashion, without a systematic account of the
differential intestinal physiology between dog and human. This project aims to elucidate
product quality differences between human and dog oral solid dosage forms as a result of the
differential physiology between the two specifies. This insight will facilitate the
regulation of canine medicines by highlighting how product standards for human medicines are
either too liberal or too restrictive for canine medicines.
Ciprofloxacin hydrochloride will be used as a model poorly soluble drug. A range of
immediate-release (IR) tablets will be formulated to map the design space. Formulations will
be fast, medium, and slow, with respect to dissolution rate of drug. Ciprofloxacin is
expected to exhibit formulation-dependent pharmacokinetics, which is additionally impacted
by the differential physiology between dog and humans. In particular, the investigators
anticipate a greater sensitivity to formulation for dogs than for humans. Consequently, the
investigators anticipate dogs to be more sensitive to formulations, where such critical
formulation factors must be considered in canine product design and regulation.
Objectives: 1) The primary objective of this human study is to assess whether specific
formulation factors impact the rate and extent of ciprofloxacin oral absorption, as well as
the absolute absorption profile of ciprofloxacin. 2) The secondary objective is to assess if
dogs exhibit a greater sensitivity to formulation than do humans.
Hypotheses: The investigators anticipate that humans exhibit a modest sensitivity to
specific tablet formulation factors. 1) Hence, the hypothesis of this human study is that
humans do not exhibit a sensitivity to specific formulation factors and show no in vitro -
in vivo correlation to dissolution rate. 2) Alternative hypothesis is that humans do exhibit
a sensitivity to specific formulation factors and show an in vitro - in vivo correlation to
dissolution rate.
Clinical Details
Official title: Impact of Formulation on Ciprofloxacin Oral Absorption
Study design: Basic Science, Randomized, Open Label, Crossover Assignment, Bio-equivalence Study
Primary outcome: The primary objective of this human study is to assess whether specific formulation factors impact the rate and extent of
ciprofloxacin oral absorption, as well as the absolute absorption profile of ciprofloxacin.
Secondary outcome: The secondary objective is to assess if dogs
exhibit a greater sensitivity to formulation than do humans
Eligibility
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Male or female
- Age 18-55
- Healthy volunteers: Subjects in good health, as determined by screening evaluation
that is not greater than 30 days before the first drug study visit
- Willing to avoid caffeine containing products 24 hours prior to and day of study
visits
- Willing to stop all OTC medications for 24 hours prior to and during study visits
- Able to provide informed consent
Exclusion Criteria:
- Presence of significant medical disease (including cardiovascular, pulmonary,
hematologic, endocrine, immunologic, neurologic, gastrointestinal or psychiatric)
- Presence of hepatic, renal disease
- Pregnant women, breast feeding or trying to become pregnant
- Excessive alcohol use (i. e. current physical, behavioral, or personal manifestations
related to the abuse or dependency on alcohol)
- Routine use (i. e. daily or weekly) prescription medication except birth control pills
- Routine use (i. e. daily or weekly) use of acid blockers, antacids, anti-diarrhea,
stimulants, appetite suppressants, or anti nausea medication or other drugs that
modulate GI function
- Currently taking ciprofloxacin or tizanidine
- Allergic to ciprofloxacin or any quinolone-type antibiotic (e. g. levofloxacin)
- Currently taking a corticosteroid drug (e. g. prednisone)
- Had a kidney, heart, or lung transplant
- Any condition in which in the opinion of the PI or medical physician would increase
risk to the subject or interfere with the integrity of the study
Locations and Contacts
James Polli, Phone: 410-706-8292, Email: jpolli@rx.umaryland.edu
University of Maryland, Baltimore, Maryland 21201, United States
Additional Information
Related publications: Polli JE, Rekhi GS, Augsburger LL, Shah VP. Methods to compare dissolution profiles and a rationale for wide dissolution specifications for metoprolol tartrate tablets. J Pharm Sci. 1997 Jun;86(6):690-700.
Starting date: December 2009
Ending date: February 2010
Last updated: October 8, 2009
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