Pharmacokinetics and clinical effects of pirfenidone administered intravenously in horses

Amy E Poulin Braim, Melinda H. MacDonald, Michael L. Bruss, Scott D Stanley, Jill K. Giri, Shri N. Giri

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective - To characterize the plasma pharmacokinetics and clinical effects of pirfenidone administered IV in healthy horses. Animals - 6 adult horses. Procedures - A 15 mg/kg dose of pirfenidone was administered IV over 5 minutes. Physical variables were recorded and blood samples collected prior to infusion; 2.5 minutes after beginning infusion; at the end of infusion; and at 3, 6, 9, 12, 15, 20, 25, 30, 40, 50, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 12, and 24 hours after completion of infusion. Plasma concentrations of pirfenidone and its metabolites were determined. Results - Mild clinical effects, including tachycardia and muscle fasciculations, were observed during drug administration but stopped at the end of the infusion. Pirfenidone and 2 metabolites, hydroxypirfenidone and carboxypirfenidone, were detected by the end of the 5-minute infusion. Mean peak plasma concentration of pirfenidone was 182.5 μmol/L, detected at the end of the infusion. Mean peak plasma concentrations of hydroxypirfenidone and carboxypirfenidone were 1.07 and 3.4 μmol/L, respectively, at 40 minutes after infusion. No parent drug or metabolites were detected at 24 hours. Distribution of pirfenidone best fit a 2-compartment model, and the drug had mean ± SEM elimination half-life of 86.0 ± 4.7 minutes, mean body clearance of 6.54 ± 0.45 mL/kg/min, and apparent volume of distribution at steady state of 0.791 ± 0.056 L/kg. Conclusions and Clinical Relevance - Intravenous administration of pirfenidone was tolerated with transient adverse affects during infusion, and drug clearance was rapid.

Original languageEnglish (US)
Pages (from-to)952-960
Number of pages9
JournalAmerican Journal of Veterinary Research
Volume69
Issue number7
DOIs
StatePublished - Jul 2008

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pharmacokinetics
Horses
Pharmacokinetics
horses
drugs
metabolites
Pharmaceutical Preparations
intravenous injection
half life
Fasciculation
muscles
pirfenidone
blood
Tachycardia
Intravenous Administration
dosage
Half-Life
animals
Muscles
sampling

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Pharmacokinetics and clinical effects of pirfenidone administered intravenously in horses. / Braim, Amy E Poulin; MacDonald, Melinda H.; Bruss, Michael L.; Stanley, Scott D; Giri, Jill K.; Giri, Shri N.

In: American Journal of Veterinary Research, Vol. 69, No. 7, 07.2008, p. 952-960.

Research output: Contribution to journalArticle

Braim, Amy E Poulin ; MacDonald, Melinda H. ; Bruss, Michael L. ; Stanley, Scott D ; Giri, Jill K. ; Giri, Shri N. / Pharmacokinetics and clinical effects of pirfenidone administered intravenously in horses. In: American Journal of Veterinary Research. 2008 ; Vol. 69, No. 7. pp. 952-960.
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abstract = "Objective - To characterize the plasma pharmacokinetics and clinical effects of pirfenidone administered IV in healthy horses. Animals - 6 adult horses. Procedures - A 15 mg/kg dose of pirfenidone was administered IV over 5 minutes. Physical variables were recorded and blood samples collected prior to infusion; 2.5 minutes after beginning infusion; at the end of infusion; and at 3, 6, 9, 12, 15, 20, 25, 30, 40, 50, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 12, and 24 hours after completion of infusion. Plasma concentrations of pirfenidone and its metabolites were determined. Results - Mild clinical effects, including tachycardia and muscle fasciculations, were observed during drug administration but stopped at the end of the infusion. Pirfenidone and 2 metabolites, hydroxypirfenidone and carboxypirfenidone, were detected by the end of the 5-minute infusion. Mean peak plasma concentration of pirfenidone was 182.5 μmol/L, detected at the end of the infusion. Mean peak plasma concentrations of hydroxypirfenidone and carboxypirfenidone were 1.07 and 3.4 μmol/L, respectively, at 40 minutes after infusion. No parent drug or metabolites were detected at 24 hours. Distribution of pirfenidone best fit a 2-compartment model, and the drug had mean ± SEM elimination half-life of 86.0 ± 4.7 minutes, mean body clearance of 6.54 ± 0.45 mL/kg/min, and apparent volume of distribution at steady state of 0.791 ± 0.056 L/kg. Conclusions and Clinical Relevance - Intravenous administration of pirfenidone was tolerated with transient adverse affects during infusion, and drug clearance was rapid.",
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N2 - Objective - To characterize the plasma pharmacokinetics and clinical effects of pirfenidone administered IV in healthy horses. Animals - 6 adult horses. Procedures - A 15 mg/kg dose of pirfenidone was administered IV over 5 minutes. Physical variables were recorded and blood samples collected prior to infusion; 2.5 minutes after beginning infusion; at the end of infusion; and at 3, 6, 9, 12, 15, 20, 25, 30, 40, 50, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 12, and 24 hours after completion of infusion. Plasma concentrations of pirfenidone and its metabolites were determined. Results - Mild clinical effects, including tachycardia and muscle fasciculations, were observed during drug administration but stopped at the end of the infusion. Pirfenidone and 2 metabolites, hydroxypirfenidone and carboxypirfenidone, were detected by the end of the 5-minute infusion. Mean peak plasma concentration of pirfenidone was 182.5 μmol/L, detected at the end of the infusion. Mean peak plasma concentrations of hydroxypirfenidone and carboxypirfenidone were 1.07 and 3.4 μmol/L, respectively, at 40 minutes after infusion. No parent drug or metabolites were detected at 24 hours. Distribution of pirfenidone best fit a 2-compartment model, and the drug had mean ± SEM elimination half-life of 86.0 ± 4.7 minutes, mean body clearance of 6.54 ± 0.45 mL/kg/min, and apparent volume of distribution at steady state of 0.791 ± 0.056 L/kg. Conclusions and Clinical Relevance - Intravenous administration of pirfenidone was tolerated with transient adverse affects during infusion, and drug clearance was rapid.

AB - Objective - To characterize the plasma pharmacokinetics and clinical effects of pirfenidone administered IV in healthy horses. Animals - 6 adult horses. Procedures - A 15 mg/kg dose of pirfenidone was administered IV over 5 minutes. Physical variables were recorded and blood samples collected prior to infusion; 2.5 minutes after beginning infusion; at the end of infusion; and at 3, 6, 9, 12, 15, 20, 25, 30, 40, 50, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 12, and 24 hours after completion of infusion. Plasma concentrations of pirfenidone and its metabolites were determined. Results - Mild clinical effects, including tachycardia and muscle fasciculations, were observed during drug administration but stopped at the end of the infusion. Pirfenidone and 2 metabolites, hydroxypirfenidone and carboxypirfenidone, were detected by the end of the 5-minute infusion. Mean peak plasma concentration of pirfenidone was 182.5 μmol/L, detected at the end of the infusion. Mean peak plasma concentrations of hydroxypirfenidone and carboxypirfenidone were 1.07 and 3.4 μmol/L, respectively, at 40 minutes after infusion. No parent drug or metabolites were detected at 24 hours. Distribution of pirfenidone best fit a 2-compartment model, and the drug had mean ± SEM elimination half-life of 86.0 ± 4.7 minutes, mean body clearance of 6.54 ± 0.45 mL/kg/min, and apparent volume of distribution at steady state of 0.791 ± 0.056 L/kg. Conclusions and Clinical Relevance - Intravenous administration of pirfenidone was tolerated with transient adverse affects during infusion, and drug clearance was rapid.

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