{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:28:35Z","timestamp":1791347315588,"version":"4.3.1"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2005,7,1]],"date-time":"2005-07-01T00:00:00Z","timestamp":1120176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Comparison of the early bactericidal activity (EBA) of rifapentine and its pharmacokinetics with those of rifampin to determine the cause of poor clinical response and regrowth between doses, leading to rifamycin monoresistance at relapse.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Determination of the dose size of rifapentine that gives sufficient drug exposure to prevent regrowth.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>EBA study over initial 5 days of treatment of 123 patients, half at Durban and half at Cape Town, who received single rifapentine doses of 300, 600, 900, or 1,200 mg rifapentine or five daily doses of 150, 300, or 600 mg rifampin, with a pharmacokinetic study on 58 patients measuring standard parameters for each dose size of rifamycin and their desacetyl metabolites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The EBAs for both rifamycins were similar, with a linear relationship to log dose at lower doses and a curvilinear response at higher doses giving a plateau at 1,136 mg rifapentine. The area under the concentration\u2013time curve (AUC) divided by the minimal inhibitory concentration (MIC) agreed well for both rifamycins on the assumption that the only free 2% of free rifapentine and the 14% of free rifampin after plasma binding were active in the lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Only the free proportions of the rifamycins were active in lesions. From consideration of the pulse size and the duration of the postantibiotic lag, a 1,200-mg dose of rifapentine seemed necessary to improve response and to prevent regrowth between doses, and hence rifamycin monoresistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.200411-1557oc","type":"journal-article","created":{"date-parts":[[2005,4,1]],"date-time":"2005-04-01T20:25:49Z","timestamp":1112387149000},"page":"128-135","source":"Crossref","is-referenced-by-count":80,"title":["The Early Bactericidal Activities of Rifampin and Rifapentine in Pulmonary Tuberculosis"],"prefix":"10.1093","volume":"172","author":[{"given":"Frik A.","family":"Sirgel","sequence":"first","affiliation":[{"name":"Lead Programme for TB Research, Medical Research Council; Department of Pediatrics and Child Health, Tygerberg; Lead Programme for TB Research, Medical Research Council, Pretoria; King George V Hospital and Unit for Clinical and Biomedical TB Research, Medical Research Council, Durban; Unit for Biostatistics, Medical Research Council, Pretoria; Division of Pharmacology, University of Cape Town, Cape Town, South Africa; FINDdiagnostics, Geneva, Switzerland; and St. George's Hospital Medical School, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Bernard","family":"Fourie","sequence":"additional","affiliation":[{"name":"Lead Programme for TB Research, Medical Research Council; Department of Pediatrics and Child Health, Tygerberg; Lead Programme for TB Research, Medical Research Council, Pretoria; King George V Hospital and Unit for Clinical and Biomedical TB Research, Medical Research Council, Durban; Unit for Biostatistics, Medical Research Council, Pretoria; Division of Pharmacology, University of Cape Town, Cape Town, South Africa; FINDdiagnostics, Geneva, Switzerland; and St. George's Hospital Medical School, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Donald","sequence":"additional","affiliation":[{"name":"Lead Programme for TB Research, Medical Research Council; Department of Pediatrics and Child Health, Tygerberg; Lead Programme for TB Research, Medical Research Council, Pretoria; King George V Hospital and Unit for Clinical and Biomedical TB Research, Medical Research Council, Durban; Unit for Biostatistics, Medical Research Council, Pretoria; Division of Pharmacology, University of Cape Town, Cape Town, South Africa; FINDdiagnostics, Geneva, Switzerland; and St. George's Hospital Medical School, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nesri","family":"Padayatchi","sequence":"additional","affiliation":[{"name":"Lead Programme for TB Research, Medical Research Council; Department of Pediatrics and Child Health, Tygerberg; Lead Programme for TB Research, Medical Research Council, Pretoria; King George V Hospital and Unit for Clinical and Biomedical TB Research, Medical Research Council, Durban; Unit for Biostatistics, Medical Research Council, Pretoria; Division of Pharmacology, University of Cape Town, Cape Town, South Africa; FINDdiagnostics, Geneva, Switzerland; and St. George's Hospital Medical School, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana","family":"Rustomjee","sequence":"additional","affiliation":[{"name":"Lead Programme for TB Research, Medical Research Council; Department of Pediatrics and Child Health, Tygerberg; Lead Programme for TB Research, Medical Research Council, Pretoria; King George V Hospital and Unit for Clinical and Biomedical TB Research, Medical Research Council, Durban; Unit for Biostatistics, Medical Research Council, Pretoria; Division of Pharmacology, University of Cape Town, Cape Town, South Africa; FINDdiagnostics, Geneva, Switzerland; and St. George's Hospital Medical School, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Levin","sequence":"additional","affiliation":[{"name":"Lead Programme for TB Research, Medical Research Council; Department of Pediatrics and Child Health, Tygerberg; Lead Programme for TB Research, Medical Research Council, Pretoria; King George V Hospital and Unit for Clinical and Biomedical TB Research, Medical Research Council, Durban; Unit for Biostatistics, Medical Research Council, Pretoria; Division of Pharmacology, University of Cape Town, Cape Town, South Africa; FINDdiagnostics, Geneva, Switzerland; and St. George's Hospital Medical School, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Roscigno","sequence":"additional","affiliation":[{"name":"Lead Programme for TB Research, Medical Research Council; Department of Pediatrics and Child Health, Tygerberg; Lead Programme for TB Research, Medical Research Council, Pretoria; King George V Hospital and Unit for Clinical and Biomedical TB Research, Medical Research Council, Durban; Unit for Biostatistics, Medical Research Council, Pretoria; Division of Pharmacology, University of Cape Town, Cape Town, South Africa; FINDdiagnostics, Geneva, Switzerland; and St. George's Hospital Medical School, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Norman","sequence":"additional","affiliation":[{"name":"Lead Programme for TB Research, Medical Research Council; Department of Pediatrics and Child Health, Tygerberg; Lead Programme for TB Research, Medical Research Council, Pretoria; King George V Hospital and Unit for Clinical and Biomedical TB Research, Medical Research Council, Durban; Unit for Biostatistics, Medical Research Council, Pretoria; Division of Pharmacology, University of Cape Town, Cape Town, South Africa; FINDdiagnostics, Geneva, Switzerland; and St. George's Hospital Medical School, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"McIlleron","sequence":"additional","affiliation":[{"name":"Lead Programme for TB Research, Medical Research Council; Department of Pediatrics and Child Health, Tygerberg; Lead Programme for TB Research, Medical Research Council, Pretoria; King George V Hospital and Unit for Clinical and Biomedical TB Research, Medical Research Council, Durban; Unit for Biostatistics, Medical Research Council, Pretoria; Division of Pharmacology, University of Cape Town, Cape Town, South Africa; FINDdiagnostics, Geneva, Switzerland; 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