Abstract
This study was performed to investigate the influence of the dosing route on chronopharmacological aspect of valproic acid (VPA) in mice, comparing the oral and rectal route. ICR male mice, housed under a standardized light-dark cycle (lights on from 0700 to 1900), were orally or rectally administered 400 mg/kg VPA each at the following scheduled time: 0900, 1300, 1700, 2100, 0100 and 0500. VPA concentrations in plasma and brain were determined by gas-liquid chromatography. There was a circadian rhythm in the electroshock seizure (ES) threshold 30 min after oral VPA administration, with the highest value at the midlight (1300) and the lowest at the middark (0100) (p<0.01). A significant circadian rhythm was also found in plasma and brain VPA concentrations 30 min after oral administration (p<0.01). This finding is related to the rhythm in the ES threshold. In contrast to oral administration, no circadian rhythm in the ESthreshold, plasma and brain VPA concentrations was observed after rectal administration. These values after rectal dosing showed higher levels in comparison to those after oral dosing. Thus, the rectal route for VPA might have merit toeliminate the time-dependent changes in VPA pharmacologic action and kinetics. The timing of drug administration is an important factor that must be carefully controlled in drug pharmacokinetic and pharmacodynamic studies and must be considered in planning dosing routes.
| Original language | English |
|---|---|
| Pages (from-to) | 403-408 |
| Number of pages | 6 |
| Journal | journal of pharmacobio-dynamics |
| Volume | 15 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Jan 1 1992 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Pharmacology
Cite this
Chronopharmacological Study of Valproic Acid in Mice : Comparison of Oral and Rectal Administration. / Yoshiyama, Yuji; Nakano, Shigeyuki; Ohdo, Shigehiro; Ogawa, Nobuya.
In: journal of pharmacobio-dynamics, Vol. 15, No. 8, 01.01.1992, p. 403-408.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Chronopharmacological Study of Valproic Acid in Mice
T2 - Comparison of Oral and Rectal Administration
AU - Yoshiyama, Yuji
AU - Nakano, Shigeyuki
AU - Ohdo, Shigehiro
AU - Ogawa, Nobuya
PY - 1992/1/1
Y1 - 1992/1/1
N2 - This study was performed to investigate the influence of the dosing route on chronopharmacological aspect of valproic acid (VPA) in mice, comparing the oral and rectal route. ICR male mice, housed under a standardized light-dark cycle (lights on from 0700 to 1900), were orally or rectally administered 400 mg/kg VPA each at the following scheduled time: 0900, 1300, 1700, 2100, 0100 and 0500. VPA concentrations in plasma and brain were determined by gas-liquid chromatography. There was a circadian rhythm in the electroshock seizure (ES) threshold 30 min after oral VPA administration, with the highest value at the midlight (1300) and the lowest at the middark (0100) (p<0.01). A significant circadian rhythm was also found in plasma and brain VPA concentrations 30 min after oral administration (p<0.01). This finding is related to the rhythm in the ES threshold. In contrast to oral administration, no circadian rhythm in the ESthreshold, plasma and brain VPA concentrations was observed after rectal administration. These values after rectal dosing showed higher levels in comparison to those after oral dosing. Thus, the rectal route for VPA might have merit toeliminate the time-dependent changes in VPA pharmacologic action and kinetics. The timing of drug administration is an important factor that must be carefully controlled in drug pharmacokinetic and pharmacodynamic studies and must be considered in planning dosing routes.
AB - This study was performed to investigate the influence of the dosing route on chronopharmacological aspect of valproic acid (VPA) in mice, comparing the oral and rectal route. ICR male mice, housed under a standardized light-dark cycle (lights on from 0700 to 1900), were orally or rectally administered 400 mg/kg VPA each at the following scheduled time: 0900, 1300, 1700, 2100, 0100 and 0500. VPA concentrations in plasma and brain were determined by gas-liquid chromatography. There was a circadian rhythm in the electroshock seizure (ES) threshold 30 min after oral VPA administration, with the highest value at the midlight (1300) and the lowest at the middark (0100) (p<0.01). A significant circadian rhythm was also found in plasma and brain VPA concentrations 30 min after oral administration (p<0.01). This finding is related to the rhythm in the ES threshold. In contrast to oral administration, no circadian rhythm in the ESthreshold, plasma and brain VPA concentrations was observed after rectal administration. These values after rectal dosing showed higher levels in comparison to those after oral dosing. Thus, the rectal route for VPA might have merit toeliminate the time-dependent changes in VPA pharmacologic action and kinetics. The timing of drug administration is an important factor that must be carefully controlled in drug pharmacokinetic and pharmacodynamic studies and must be considered in planning dosing routes.
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U2 - 10.1248/bpb1978.15.403
DO - 10.1248/bpb1978.15.403
M3 - Article
VL - 15
SP - 403
EP - 408
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
SN - 0918-6158
IS - 8
ER -