Effects of Ticlopidine on the Pharmacokinetics of Diltiazem and Its Main Metabolite, Desacetyldiltiazem, in Rats

In Vitro Assessment of the Interaction Potential of Ocimum basilicum (L.) Extracts on CYP2B6, 3A4, and Rifampicin Metabolism

“…At concentrations >100 mg/ml, the IC 50 curve did not show a drop in the percentage of remaining activity, unlike the 2-point screening (percentage activity drop from 81.7% at 20 mg/ml to 36.97% 200 mg/ml) indicating the latter to be a relative measurement of the inhibitory effect of an extract at two different concentrations, which would not always correlate with the IC 50 value obtained. For the positive control ticlopidine the IC 50 value obtained was within the range reported in earlier studies (12.4-55 mM) (Hagihara et al, 2008;Choi et al, 2011). For nelfinavir the IC 50 was slightly higher than a value of 2.7 mM reported in a previous HLM study done using different assay conditions and bilirubin as the substrate (Zhang et al, 2005).…”

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

“…23 Diltiazem undergoes extensive phase I metabolism including desacetylation, N-demethylation, and O-demethylation in rats. 32 Kinetically, the unbound drug concentration of a drug in an eliminating organ (such as liver) is also expected to be lower than that in blood, when the drug is subject to an extensive cell metabolism. 3,5 Although antipyrine, lamotrigine and carbamazepine are also largely metabolized in the liver, the K puu,liver values of these compounds are close to 1 because these compounds have low CL (4.81, 1.48 and 18.1 ml/min/kg, respectively) and are not subject to an extensive hepatic metabolism in rats.…”

“… 23 Diltiazem undergoes extensive phase I metabolism including desacetylation, N‐demethylation, and O‐demethylation in rats. 32 Kinetically, the unbound drug concentration of a drug in an eliminating organ (such as liver) is also expected to be lower than that in blood, when the drug is subject to an extensive cell metabolism. 3 , 5 …”

“…A rat study has revealed that diltiazem was subject to an extensive hepatic first‐pass metabolism, and only about 30% of the dose reached the systemic circulation, when it was injected directly into the portal vein in rats 23 . Diltiazem undergoes extensive phase I metabolism including desacetylation, N‐demethylation, and O‐demethylation in rats 32 . Kinetically, the unbound drug concentration of a drug in an eliminating organ (such as liver) is also expected to be lower than that in blood, when the drug is subject to an extensive cell metabolism 3,5 …”