Analysis of the Transport of Valproic Acid into Saliva from Serum

• Published in: Biological & pharmaceutical bulletin Vol. 17; no. 2; pp. 340 - 344
• Main Authors: SUZUKI, Yoshinari, UEMATSU, Toshihiko, MIZUNO, Atsuhiro, NINCHOJI, Toshiaki, FUJII, Kiichiro, NAKASHIMA, Mitsuyoshi
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01-02-1994; Maruzen; Japan Science and Technology Agency
• Subjects: Adolescent; Adult; Aged; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Child; Diffusion; Epilepsy - metabolism; Female; Humans; Male; Mathematics; Medical sciences; Microvilli - metabolism; Middle Aged; Neuropharmacology; Pharmacology. Drug treatments; saliva; Saliva - metabolism; serum; TDM; transport; valproic acid; Valproic Acid - blood; Valproic Acid - metabolism; Valproic Acid - pharmacokinetics; Human; Nervous system diseases; Computer simulation; Epilepsy; Biological transport; Anticonvulsant; Cerebral disorder; Central nervous system disease; Serum; Diffusion; Mathematical model; Pharmacokinetics; Saliva
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.17.340

A study was conducted to explore whether a positive correlation between serum and salivary concentrations of the well-known antiepileptic drug, valproic acid (VPA), in epileptic patients could be explained by facilitated diffusion. The total concentration in saliva (Cs) would be related to the apparent ratio (Rapp=100·Cs/Ct) of Cs to the total concentration in serum (Ct) as follows : Cs=A·Rapp+B. This equation can be illustrated with microcomputer-simulated figures by assuming a process of facilitated diffusion for the transport of VPA into saliva from blood by the mechanism of monocarboxylic acid absorption through the intestinal brush-border membrane vesicles. The above equation has been proved to be valid when applied to the data reported separately by Gugler and coworkers and by Nitsche and Mascher, who evaluated the pharmacokinetics of VPA. Moreover, we can estimate the serum concentration with the salivary concentration using the above equation.