Population pharmacokinetics and pharmacodynamics of ofloxacin in South African patients with multidrug-resistant tuberculosis

Emmanuel Chigutsa, Sandra Meredith, Lubbe Wiesner, Nesri Padayatchi, Joe Harding, Prashini Moodley, William R Mac Kenzie, Marc H Weiner, Helen McIlleron, Carl M J Kirkpatrick

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Despite the important role of fluoroquinolones and the predominant use of ofloxacin for treating multidrug-resistant tuberculosis in South Africa, there are limited data on ofloxacin pharmacokinetics in patients with multidrug-resistant tuberculosis, no ofloxacin pharmacokinetic data from South African patients, and no direct assessment of the relationship between ofloxacin pharmacokinetics and the MIC of ofloxacin of patient isolates. Our objectives are to describe ofloxacin pharmacokinetics in South African patients being treated for multidrug-resistant tuberculosis and assess the adequacy of ofloxacin drug exposure with respect to the probability of pharmacodynamic target attainment (area under the time curve/MIC ratio of at least 100). Sixty-five patients with multidrug-resistant tuberculosis were recruited from 2 hospitals in South Africa. We determined the ofloxacin MICs for the Mycobacterium tuberculosis isolates from baseline sputum specimens. Patients received daily doses of 800 mg ofloxacin, in addition to other antitubercular drugs. Patients underwent pharmacokinetic sampling at steady state. NONMEM was used for data analysis. The population pharmacokinetics of ofloxacin in this study has been adequately described. The probability of target attainment expectation in the study population was 0.45. Doubling the dose to 1,600 mg could increase this to only 0.77. The currently recommended ofloxacin dose appeared inadequate for the majority of this study population. Studies to assess the tolerability of higher doses are warranted. Alternatively, ofloxacin should be replaced with more potent fluoroquinolones.

Original languageEnglish (US)
Pages (from-to)3857-3863
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume56
Issue number7
DOIs
StatePublished - Jul 2012
Externally publishedYes

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Multidrug-Resistant Tuberculosis
Ofloxacin
Pharmacokinetics
Population
Fluoroquinolones
South Africa
Antitubercular Agents
Sputum
Mycobacterium tuberculosis
Area Under Curve

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases

Cite this

Chigutsa, E., Meredith, S., Wiesner, L., Padayatchi, N., Harding, J., Moodley, P., ... Kirkpatrick, C. M. J. (2012). Population pharmacokinetics and pharmacodynamics of ofloxacin in South African patients with multidrug-resistant tuberculosis. Antimicrobial Agents and Chemotherapy, 56(7), 3857-3863. https://doi.org/10.1128/AAC.00048-12

Population pharmacokinetics and pharmacodynamics of ofloxacin in South African patients with multidrug-resistant tuberculosis. / Chigutsa, Emmanuel; Meredith, Sandra; Wiesner, Lubbe; Padayatchi, Nesri; Harding, Joe; Moodley, Prashini; Kenzie, William R Mac; Weiner, Marc H; McIlleron, Helen; Kirkpatrick, Carl M J.

In: Antimicrobial Agents and Chemotherapy, Vol. 56, No. 7, 07.2012, p. 3857-3863.

Research output: Contribution to journalArticle

Chigutsa, E, Meredith, S, Wiesner, L, Padayatchi, N, Harding, J, Moodley, P, Kenzie, WRM, Weiner, MH, McIlleron, H & Kirkpatrick, CMJ 2012, 'Population pharmacokinetics and pharmacodynamics of ofloxacin in South African patients with multidrug-resistant tuberculosis', Antimicrobial Agents and Chemotherapy, vol. 56, no. 7, pp. 3857-3863. https://doi.org/10.1128/AAC.00048-12
Chigutsa, Emmanuel ; Meredith, Sandra ; Wiesner, Lubbe ; Padayatchi, Nesri ; Harding, Joe ; Moodley, Prashini ; Kenzie, William R Mac ; Weiner, Marc H ; McIlleron, Helen ; Kirkpatrick, Carl M J. / Population pharmacokinetics and pharmacodynamics of ofloxacin in South African patients with multidrug-resistant tuberculosis. In: Antimicrobial Agents and Chemotherapy. 2012 ; Vol. 56, No. 7. pp. 3857-3863.
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