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Pharmacokinetic/pharmacodynamic (PK/PD) evaluation of a once-daily treatment using ciprofloxacin in an extended-release dosage form.
Infection. 2005 Dec; 33 Suppl 2:22-8.I

Abstract

OBJECTIVE

To evaluate the suitability of a once-a-day dosing regimen of ciprofloxacin using a new extended-release dosage form based on PK/PD principles.

METHODS

Ciprofloxacin's serum concentrations were measured after administration of 500 mg immediate-release twice-daily, and 1,000 mg extended-release once-daily to 19 healthy volunteers. Pharmacokinetic parameters were determined using non-compartmental and compartmental data analysis. Measured serum concentration profiles were linked to ciprofloxacin's effect against Escherichia coli (MIC 0.013 mg/l) from in vitro kill curve studies where the pharmacokinetics of ciprofloxacin were simulated and change in number of bacteria (CFU/ml) versus time was monitored. Resulting parameters were used to compare expected kill curves for the two dosing regimens based on measured ciprofloxacin concentrations.

RESULTS

Fitting the data using an appropriate PK/PD model resulted in a set of mean pharmacodynamic parameters (bacterial growth rate constant, k0, maximum kill rate constant, Kmax, and EC50). The model included a novel term to account for a change in kill rate after approximately 4 h when Kmax decreased in concentration-dependent matter. The model allowed excellent curve fits of all ciprofloxacin concentrations investigated. Comparison of expected kill curves with the immediate-release versus extended-release treatments showed similar outcome. Both treatments resulted in a decrease in CFU/ml > 5 log units over 24 h.

CONCLUSION

Results indicate that once-a-day dosing of equal total daily doses with the new and more compliance-friendly extended-release dosing form will be therapeutically equivalent to once-a-day dosing with traditional immediate-release dosage forms for treatment of infections with this microorganism.

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Publisher Full Text

Authors+Show Affiliations

Schuck EL
Dept. of Pharmaceutics, PO 100494, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
Dalhoff A
No affiliation info available
Stass H
No affiliation info available
Derendorf H
No affiliation info available

MeSH

AdultAnti-Bacterial AgentsArea Under CurveCiprofloxacinCross-Over StudiesDelayed-Action PreparationsDrug Administration ScheduleHalf-LifeHumansMaleMiddle AgedModels, BiologicalRandom Allocation

Pub Type(s)

Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16518708

Citation

Schuck, E L., et al. "Pharmacokinetic/pharmacodynamic (PK/PD) Evaluation of a Once-daily Treatment Using Ciprofloxacin in an Extended-release Dosage Form." Infection, vol. 33 Suppl 2, 2005, pp. 22-8.
Schuck EL, Dalhoff A, Stass H, et al. Pharmacokinetic/pharmacodynamic (PK/PD) evaluation of a once-daily treatment using ciprofloxacin in an extended-release dosage form. Infection. 2005;33 Suppl 2:22-8.
Schuck, E. L., Dalhoff, A., Stass, H., & Derendorf, H. (2005). Pharmacokinetic/pharmacodynamic (PK/PD) evaluation of a once-daily treatment using ciprofloxacin in an extended-release dosage form. Infection, 33 Suppl 2, 22-8.
Schuck EL, et al. Pharmacokinetic/pharmacodynamic (PK/PD) Evaluation of a Once-daily Treatment Using Ciprofloxacin in an Extended-release Dosage Form. Infection. 2005;33 Suppl 2:22-8. PubMed PMID: 16518708.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetic/pharmacodynamic (PK/PD) evaluation of a once-daily treatment using ciprofloxacin in an extended-release dosage form. AU - Schuck,E L, AU - Dalhoff,A, AU - Stass,H, AU - Derendorf,H, PY - 2006/3/7/pubmed PY - 2006/7/1/medline PY - 2006/3/7/entrez SP - 22 EP - 8 JF - Infection JO - Infection VL - 33 Suppl 2 N2 - OBJECTIVE: To evaluate the suitability of a once-a-day dosing regimen of ciprofloxacin using a new extended-release dosage form based on PK/PD principles. METHODS: Ciprofloxacin's serum concentrations were measured after administration of 500 mg immediate-release twice-daily, and 1,000 mg extended-release once-daily to 19 healthy volunteers. Pharmacokinetic parameters were determined using non-compartmental and compartmental data analysis. Measured serum concentration profiles were linked to ciprofloxacin's effect against Escherichia coli (MIC 0.013 mg/l) from in vitro kill curve studies where the pharmacokinetics of ciprofloxacin were simulated and change in number of bacteria (CFU/ml) versus time was monitored. Resulting parameters were used to compare expected kill curves for the two dosing regimens based on measured ciprofloxacin concentrations. RESULTS: Fitting the data using an appropriate PK/PD model resulted in a set of mean pharmacodynamic parameters (bacterial growth rate constant, k0, maximum kill rate constant, Kmax, and EC50). The model included a novel term to account for a change in kill rate after approximately 4 h when Kmax decreased in concentration-dependent matter. The model allowed excellent curve fits of all ciprofloxacin concentrations investigated. Comparison of expected kill curves with the immediate-release versus extended-release treatments showed similar outcome. Both treatments resulted in a decrease in CFU/ml > 5 log units over 24 h. CONCLUSION: Results indicate that once-a-day dosing of equal total daily doses with the new and more compliance-friendly extended-release dosing form will be therapeutically equivalent to once-a-day dosing with traditional immediate-release dosage forms for treatment of infections with this microorganism. SN - 0300-8126 UR - https://www.unboundmedicine.com/medline/citation/16518708/Pharmacokinetic/pharmacodynamic__PK/PD__evaluation_of_a_once_daily_treatment_using_ciprofloxacin_in_an_extended_release_dosage_form_ L2 - https://doi.org/10.1007/s15010-005-8204-0 DB - PRIME DP - Unbound Medicine ER -