Pharmacokinetics of para-aminosalicylic acid granules under four dosing conditions

C. A. Peloquin, M. Zhu, R. D. Adam, M. D. Singleton, David E. Nix

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

OBJECTIVE: To determine the pharmacokinetics and relative bioavailability of para-aminosalicylic acid (PAS) granules. DESIGN: Phase I pharmacokinetics study. SETTING: University of Arizona School of Pharmacy. PARTICIPANTS: Sixteen healthy male and female volunteers aged 36 ± 8 years. INTERVENTIONS: Subjects received single doses of PAS granules (6 g) combined with cycloserine 500 mg, clofazimine 200 mg, ethionamide 500 mg, and pyridoxine 100 mg. Drugs were given on an empty stomach after an overnight fast (reference) with high-fat food, with orange juice, and with antacids. MEASUREMENTS AND RESULTS: Four subjects did not complete all four treatments due to adverse events or personal reasons. Plasma and urine samples were collected for 48 hours and measured by a validated HPLC assay. Pharmacokinetic data analysis was performed with WinNonlin using noncompartmental methods and a one-compartmental model. Bioequivalence testing was performed using the mean ratios of the maximum concentrations (Cmax) and AUC0-∞ of PAS, with 90% confidence intervals. Compared with the fasted condition, food increased Cmax 1.5-fold and AUC0-∞ 1.7-fold, and it doubled the time to maximum concentration (tmax). The least-squares mean ratios (treatment/reference) for Cmax were 0.90 (58% to 139% CI), 1.16 (75% to 179% CI), and 0.82 (52% to 127% CI) with orange juice, food, or antacid treatment, respectively. Corresponding ratios for AUC0-∞ were 1.05 (71% to 155% CI), 1.52 (103% to 224% CI), and 0.84 (57% to 125% CI), respectively. CONCLUSIONS: Food significantly enhanced the absorption of PAS, while orange juice and antacids had minor effects.

Original languageEnglish (US)
Pages (from-to)1332-1338
Number of pages7
JournalAnnals of Pharmacotherapy
Volume35
Issue number11
StatePublished - 2001
Externally publishedYes

Fingerprint

Aminosalicylic Acid
Antacids
Pharmacokinetics
Food
Ethionamide
Clofazimine
Pharmacy Schools
Cycloserine
Pyridoxine
Therapeutic Equivalency
Least-Squares Analysis
Biological Availability
Volunteers
Stomach
Therapeutics
Fats
High Pressure Liquid Chromatography
Urine
Confidence Intervals
Pharmaceutical Preparations

Keywords

  • Para-aminosalicylic acid
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Peloquin, C. A., Zhu, M., Adam, R. D., Singleton, M. D., & Nix, D. E. (2001). Pharmacokinetics of para-aminosalicylic acid granules under four dosing conditions. Annals of Pharmacotherapy, 35(11), 1332-1338.

Pharmacokinetics of para-aminosalicylic acid granules under four dosing conditions. / Peloquin, C. A.; Zhu, M.; Adam, R. D.; Singleton, M. D.; Nix, David E.

In: Annals of Pharmacotherapy, Vol. 35, No. 11, 2001, p. 1332-1338.

Research output: Contribution to journalArticle

Peloquin, CA, Zhu, M, Adam, RD, Singleton, MD & Nix, DE 2001, 'Pharmacokinetics of para-aminosalicylic acid granules under four dosing conditions', Annals of Pharmacotherapy, vol. 35, no. 11, pp. 1332-1338.
Peloquin, C. A. ; Zhu, M. ; Adam, R. D. ; Singleton, M. D. ; Nix, David E. / Pharmacokinetics of para-aminosalicylic acid granules under four dosing conditions. In: Annals of Pharmacotherapy. 2001 ; Vol. 35, No. 11. pp. 1332-1338.
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abstract = "OBJECTIVE: To determine the pharmacokinetics and relative bioavailability of para-aminosalicylic acid (PAS) granules. DESIGN: Phase I pharmacokinetics study. SETTING: University of Arizona School of Pharmacy. PARTICIPANTS: Sixteen healthy male and female volunteers aged 36 ± 8 years. INTERVENTIONS: Subjects received single doses of PAS granules (6 g) combined with cycloserine 500 mg, clofazimine 200 mg, ethionamide 500 mg, and pyridoxine 100 mg. Drugs were given on an empty stomach after an overnight fast (reference) with high-fat food, with orange juice, and with antacids. MEASUREMENTS AND RESULTS: Four subjects did not complete all four treatments due to adverse events or personal reasons. Plasma and urine samples were collected for 48 hours and measured by a validated HPLC assay. Pharmacokinetic data analysis was performed with WinNonlin using noncompartmental methods and a one-compartmental model. Bioequivalence testing was performed using the mean ratios of the maximum concentrations (Cmax) and AUC0-∞ of PAS, with 90{\%} confidence intervals. Compared with the fasted condition, food increased Cmax 1.5-fold and AUC0-∞ 1.7-fold, and it doubled the time to maximum concentration (tmax). The least-squares mean ratios (treatment/reference) for Cmax were 0.90 (58{\%} to 139{\%} CI), 1.16 (75{\%} to 179{\%} CI), and 0.82 (52{\%} to 127{\%} CI) with orange juice, food, or antacid treatment, respectively. Corresponding ratios for AUC0-∞ were 1.05 (71{\%} to 155{\%} CI), 1.52 (103{\%} to 224{\%} CI), and 0.84 (57{\%} to 125{\%} CI), respectively. CONCLUSIONS: Food significantly enhanced the absorption of PAS, while orange juice and antacids had minor effects.",
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N2 - OBJECTIVE: To determine the pharmacokinetics and relative bioavailability of para-aminosalicylic acid (PAS) granules. DESIGN: Phase I pharmacokinetics study. SETTING: University of Arizona School of Pharmacy. PARTICIPANTS: Sixteen healthy male and female volunteers aged 36 ± 8 years. INTERVENTIONS: Subjects received single doses of PAS granules (6 g) combined with cycloserine 500 mg, clofazimine 200 mg, ethionamide 500 mg, and pyridoxine 100 mg. Drugs were given on an empty stomach after an overnight fast (reference) with high-fat food, with orange juice, and with antacids. MEASUREMENTS AND RESULTS: Four subjects did not complete all four treatments due to adverse events or personal reasons. Plasma and urine samples were collected for 48 hours and measured by a validated HPLC assay. Pharmacokinetic data analysis was performed with WinNonlin using noncompartmental methods and a one-compartmental model. Bioequivalence testing was performed using the mean ratios of the maximum concentrations (Cmax) and AUC0-∞ of PAS, with 90% confidence intervals. Compared with the fasted condition, food increased Cmax 1.5-fold and AUC0-∞ 1.7-fold, and it doubled the time to maximum concentration (tmax). The least-squares mean ratios (treatment/reference) for Cmax were 0.90 (58% to 139% CI), 1.16 (75% to 179% CI), and 0.82 (52% to 127% CI) with orange juice, food, or antacid treatment, respectively. Corresponding ratios for AUC0-∞ were 1.05 (71% to 155% CI), 1.52 (103% to 224% CI), and 0.84 (57% to 125% CI), respectively. CONCLUSIONS: Food significantly enhanced the absorption of PAS, while orange juice and antacids had minor effects.

AB - OBJECTIVE: To determine the pharmacokinetics and relative bioavailability of para-aminosalicylic acid (PAS) granules. DESIGN: Phase I pharmacokinetics study. SETTING: University of Arizona School of Pharmacy. PARTICIPANTS: Sixteen healthy male and female volunteers aged 36 ± 8 years. INTERVENTIONS: Subjects received single doses of PAS granules (6 g) combined with cycloserine 500 mg, clofazimine 200 mg, ethionamide 500 mg, and pyridoxine 100 mg. Drugs were given on an empty stomach after an overnight fast (reference) with high-fat food, with orange juice, and with antacids. MEASUREMENTS AND RESULTS: Four subjects did not complete all four treatments due to adverse events or personal reasons. Plasma and urine samples were collected for 48 hours and measured by a validated HPLC assay. Pharmacokinetic data analysis was performed with WinNonlin using noncompartmental methods and a one-compartmental model. Bioequivalence testing was performed using the mean ratios of the maximum concentrations (Cmax) and AUC0-∞ of PAS, with 90% confidence intervals. Compared with the fasted condition, food increased Cmax 1.5-fold and AUC0-∞ 1.7-fold, and it doubled the time to maximum concentration (tmax). The least-squares mean ratios (treatment/reference) for Cmax were 0.90 (58% to 139% CI), 1.16 (75% to 179% CI), and 0.82 (52% to 127% CI) with orange juice, food, or antacid treatment, respectively. Corresponding ratios for AUC0-∞ were 1.05 (71% to 155% CI), 1.52 (103% to 224% CI), and 0.84 (57% to 125% CI), respectively. CONCLUSIONS: Food significantly enhanced the absorption of PAS, while orange juice and antacids had minor effects.

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