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Free Valproic Acid: Steady-State Pharmacokinetics in Patients with Intractable Epilepsy

Published online by Cambridge University Press:  18 September 2015

N. Otten ,
K. Hall ,
J. Irvine-Meek ,
M. Leroux ,
D. Budnik  and
S. Seshia
N. Otten*
Affiliation:
the Departments of Pharmaceutical Services, (Drs. Otten, Hall, and Irvine-Meek), Clinical Chemistry, (Mr. Leroux and Ms. Budnik). and Pediatrics, (Dr. Seshia), Health Sciences Centre and University of Manitoba
K. Hall
Affiliation:
the Departments of Pharmaceutical Services, (Drs. Otten, Hall, and Irvine-Meek), Clinical Chemistry, (Mr. Leroux and Ms. Budnik). and Pediatrics, (Dr. Seshia), Health Sciences Centre and University of Manitoba
J. Irvine-Meek
Affiliation:
the Departments of Pharmaceutical Services, (Drs. Otten, Hall, and Irvine-Meek), Clinical Chemistry, (Mr. Leroux and Ms. Budnik). and Pediatrics, (Dr. Seshia), Health Sciences Centre and University of Manitoba
M. Leroux
Affiliation:
the Departments of Pharmaceutical Services, (Drs. Otten, Hall, and Irvine-Meek), Clinical Chemistry, (Mr. Leroux and Ms. Budnik). and Pediatrics, (Dr. Seshia), Health Sciences Centre and University of Manitoba
D. Budnik
Affiliation:
the Departments of Pharmaceutical Services, (Drs. Otten, Hall, and Irvine-Meek), Clinical Chemistry, (Mr. Leroux and Ms. Budnik). and Pediatrics, (Dr. Seshia), Health Sciences Centre and University of Manitoba
S. Seshia
Affiliation:
the Departments of Pharmaceutical Services, (Drs. Otten, Hall, and Irvine-Meek), Clinical Chemistry, (Mr. Leroux and Ms. Budnik). and Pediatrics, (Dr. Seshia), Health Sciences Centre and University of Manitoba
*
Department of Pharmaceutical Services, General Hospital, 700 William Avenue, Winnipeg, Manitoba, Canada R3E 0Z3
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Abstract

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Free and total valproic acid (VPA) pharmacokinetic evaluation was carried out at steady state in six young epileptics who were also receiving other anticonvulsants. Subjects received their usual morning dose of VPA after an overnight fast. Blood samples for free and total VPA were taken prior to the dose and frequently thereafter for 12 hours. The calculated pharmacokinetic parameters for total VPA and free VPA were: half-lives of 7.5 ± 1.6 hours and 5.0 ± 1.5 hours, volumes of distribution of 0.189 ± 0.038 l/kg and 1.51 ± 0.98 l/kg, and clearances of 0.30 ± 0.06 and 3.6 ± 2.0 ml/min/kg., respectively. There was a strong correlation between percent free VPA and total VPA (r = 0.81) but marked inter- and intra-subject variations were seen. Studies attempting to correlate VPA levels to clinical response must take such data into account.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 11 , Issue 4 , November 1984 , pp. 457 - 460
Copyright
Copyright © Canadian Neurological Sciences Federation 1984

References

Bowdle, TA., Patel, IH., Levy, RH., Wilensky, AJ. (1980) Valproic Acid dosage and plasma protein binding and clearance. Clin Pharmacol Ther 28: 486–492.CrossRefGoogle ScholarPubMed
Bruni, J., Gallo, JM., Wilder, BJ. (1979) Effect of phenytoin on protein binding of valproic acid. Can J Neurol Sci 6: 453–454.CrossRefGoogle ScholarPubMed
Cloyd, JC., Kriel, RL., Fischer, JH., Sawchuk, RJ., Eggerth, RM. (1983). Pharmacokinetics of valproic acid in children: I. Multiple antiepileptic drug therapy. Neurology 33: 185–191.CrossRefGoogle ScholarPubMed
Cramer, JA., Mattson, RH. (1979) Valproic Acid: In Vitro plasma protein binding and interaction with phenytoin. Ther Drug Monit 1: 105–116.CrossRefGoogle ScholarPubMed
Fleitman, JS., Bruni, J., Perrin, JH., Wilder, BJ. (1980) Albumin interactions of sodium valproate. J Clin Pharmacol 20: 514–517.CrossRefGoogle ScholarPubMed
Gugler, R., von Unruh, GE:Clinical pharmacokinetics of valproic acid (1980). Clin Pharmacokinet 5: 67–83.CrossRefGoogle ScholarPubMed
Hall, K., Otten, N., Irvine-Meek, J., Leroux, M., Budnik, D., Verma, M., Seshia, SS. (1983) First dose and steady state pharmacokinetics of valproic acid in children with seizures. Clin Pharmacokinet 8: 447–455.CrossRefGoogle ScholarPubMed
Joern, WA. (1981) Gas chromatographic assay of free phenytoin in ultra filtrates of plasma: test of a new filtration apparatus and specimen stability. Clin Chem 27: 417–421.CrossRefGoogle ScholarPubMed
Klotz, U., Antonin, K. (1977) Pharmacokinetics and bioavailability of sodium valproate. Clin Pharmacol Ther 21: 736–743.CrossRefGoogle ScholarPubMed
Leroux, M., Budnick, D., Hall, K., Irvine-Meek, J., Otten, N., Seshia, SS. (1981) Comparison of gas-liquid chromatography and EMIT assay for serum valproic acid. Clin Biochem 14: 87–90.CrossRefGoogle ScholarPubMed
Levy, RH. (1980) Monitoring of free valproic acid levels? Ther. Drug Monit 2: 199–201.CrossRefGoogle Scholar
Marty, JJ., Kilpatrick, CJ., Moulds, RFW. (1982) Intra-dose variation in plasma protein binding of sodium valproate in epileptic patients. Br J Clin Pharmacol 14: 399–404.CrossRefGoogle ScholarPubMed
Mattson, GF., Mattson, RH., Cramer, J. (1982) Interaction between valproic acid and carbamazepine: An in vitro study of protein binding. Ther Drug Monit 4: 181–184.CrossRefGoogle Scholar
Monks, A., Boobis, S., Nadsworth, J., Richens, A. (1978) Plasma protein binding interaction between phenytoin and valproic acid in vitro. Br J Clin Pharmacol 6: 487–492.CrossRefGoogle ScholarPubMed
Patel, IH., Levy, RH. (1979) Valproic Acid binding to human serum albumin and determination of free fraction in the presence of anticonvulsants and free fatty acids. Epilepsia 20: 85–90.CrossRefGoogle ScholarPubMed
Perucca, E., Gatti, G., Frigo, G., Crema, A. (1978) Pharmacokinetics of valproic acid after oral and intravenous administration. Br J Clin Pharmacol 5: 313–318.CrossRefGoogle Scholar
Perucca, E. (1984) Free level monitoring of antiepileptic drugs. Clin Pharmacokinet 9 (supplement 1): 71–78.CrossRefGoogle ScholarPubMed
Roman, EJ., Ponniah, P., Lambert, JB., Buchanan, N. (1982) Free sodium valproate monitoring. Bri J Clin Pharmacol 13: 452–454.CrossRefGoogle ScholarPubMed
Ruprah, M., Perucca, E., Richens, A. (1981) Spuriously high values of unbound drug fraction in serum as determined by the new ultrafree anticonvulsant drug filters. Br J Pharmacol 12: 753–756.CrossRefGoogle ScholarPubMed