The influence of chronic verapamil treatment on antipyrine elimination was studied in eight angina patients. Antipyrine half-life (mean +/- s.d.) was 13.1 +/- 1.15 h at the start of therapy and 16.6 +/- 3.05 h (P less than 0.05) during chronic oral administration of verapamil (80-120 mg four or three times daily for 4 to 7 months). There was a significant decrease in antipyrine clearance (mean +/- s.d, 43.2 +/- 16.8 ml min-1 vs 28.7 +/- 16.6 ml min-1, P less than 0.01) while the change of distribution volume was insignificant. Verapamil elimination was also found to be impaired after chronic dosing as compared to single administration. Half-lives measured from the concentration vs time and urinary excretion rate vs time curves were both prolonged and oral clearance was decreased. Our results suggest that the inhibition of drug-metabolizing enzymes accounts for the impairment of verapamil elimination on chronic administration.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1401172 | PMC |
| http://dx.doi.org/10.1111/j.1365-2125.1986.tb02942.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
In vivo systemic evaluation of nasal drug absorption from powder formulations in rats.
Eur J Pharm Biopharm
December 2024
Laboratory of Pharmaceutical Technology, Kobe Pharmaceutical University, 4-19-1 Motoyamakitamachi, Higashinada-ku, Kobe, Hyogo 658-8558, Japan.
Despite the potential benefits of nasal drug delivery, there is a need for a systematic evaluation of the efficacy of powder formulations adhering to the nasal mucosa. This study aims to establish a systematic evaluation method for nasal drug absorption from powder formulations. We selected three model compounds-antipyrine, griseofulvin, and acyclovir-and analyzed their pharmacokinetics following nasal administration of powder formulations under physiological conditions.
View Article and Find Full Text PDFEdaravone Oral Suspension: A Neuroprotective Agent to Treat Amyotrophic Lateral Sclerosis.
Am J Ther
May 2024
Faculty of Medicine, Transilvania University of Brasov, Brasov, Romania.
Background: Amyotrophic lateral sclerosis (ALS) is characterized by loss of motor neurons due to degeneration of nerve cells within the brain and spinal cord. Early symptoms include limb weakness, twitching or muscle cramping, and slurred speech. As the disease progresses, difficulty breathing, swallowing, and paralysis can lead to death.
View Article and Find Full Text PDFUnderstanding the Mechanism and Extent of Transplacental Transfer of (-)-∆ -Tetrahydrocannabinol (THC) in the Perfused Human Placenta to Predict In Vivo Fetal THC Exposure.
Clin Pharmacol Ther
August 2023
Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
Cannabis use during pregnancy may cause fetal toxicity driven by in utero exposure to (-)-∆ -tetrahydrocannabinol (THC) and its psychoactive metabolite, (±)-11-hydroxy-∆ -THC (11-OH-THC). THC concentrations in the human term fetal plasma appear to be lower than the corresponding maternal concentrations. Therefore, we investigated whether THC and its metabolites are effluxed by placental transporters using the dual cotyledon, dual perfusion, term human placenta.
View Article and Find Full Text PDFEffect of Excessive Serotonin on Pharmacokinetics of Cephalexin after Oral Administration: Studies with Serotonin-Excessive Model Rats.
Pharm Res
September 2022
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama, 700-8530, Japan.
Purpose: Serotonin (5-HT) is important for gastrointestinal functions, but its role in drug absorption remains to be clarified. Therefore, the pharmacokinetics and oral absorption of cephalexin (CEX) were examined under 5-HT-excessive condition to understand the role of 5-HT.
Methods: 5-HT-excessive rats were prepared by multiple intraperitoneal dosing of 5-HT and clorgyline, an inhibitor for 5-HT metabolism, and utilized to examine the pharmacokinetics, absorption behavior and the intestinal permeability for CEX.
Effects of membrane transport activity and cell metabolism on the unbound drug concentrations in the skeletal muscle and liver of drugs: A microdialysis study in rats.
Pharmacol Res Perspect
October 2021
DMPK Department, Pharmaron Inc., Beijing, China.
The unbound concentrations of 14 commercial drugs, including five non-efflux/uptake transporter substrates-Class I, five efflux transporter substrates-class II and four influx transporter substrates-Class III, were simultaneously measured in rat liver, muscle, and blood via microanalysis. K and K were calculated to evaluate the membrane transport activity and cell metabolism on the unbound drug concentrations in the skeletal muscle and liver. For Class I compounds, represented by antipyrine, unbound concentrations among liver, muscle and blood are symmetrically distributed when compound hepatic clearance is low.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!