Relationship between systemic drug absorption and gastrointestinal transit after the simultaneous oral administration of carbamazepine as a controlled‐release system and as a suspension of 15N‐labelled drug to healthy volunteers.

Abstract

1. Plasma drug concentrations after a single oral administration of a suspension of carbamazepine (CBZ) and a 20/200 CBZ Oros osmotic pump system were measured in eight healthy male volunteers. The oral suspension contained 100 mg CBZ labelled with the stable isotope nitrogen‐15, whilst the Oros contained 200 mg unlabelled CBZ. Plasma concentrations of [15N]‐CBZ and CBZ were measured simultaneously by gas chromatography‐mass spectrometry. 2. The position of the CBZ Oros (labelled with indium‐111) in the gastrointestinal tract was followed by gamma scintigraphy. Plasma drug concentrations after the two treatments were used to relate pharmacokinetic with transit data. 3. The Oros was taken after breakfast and gastric emptying occurred between 1.1‐ greater than h post‐dosing (median, 5.3 h). Small intestinal transit times ranged from 1.5‐ greater than 3.6 h, with a median of 2.2 h. There were wide individual variations in colonic transit, and the total transit time ranged from 10‐60 h (median, 22 h). 4. Relative systemic bioavailability of CBZ from the Oros was reduced compared with that from the suspension (mean dose normalised AUC ratio = 0.69 +/‐ 0.17; mean dose‐normalised AUC ratio = 0.85 +/‐ 0.13, allowing for actual release from the Oros system). 5. The in vivo absorption of drug into the systemic circulation from the Oros was estimated using the Wagner‐Nelson method. This showed that absorption of CBZ was rapid when the Oros was present in the stomach and small intestine, the rate being determined by the release of drug from the system.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetic Variability of Long-Acting Stimulants in the Treatment of Children and Adults with Attention-Deficit Hyperactivity Disorder

“…The residual amount of drug in excreted OROS Ò systems was inversely proportional to transit time. [82] In several studies, median total gastrointestinal transit time was approximately 22-27 hours, but varied widely from patient to patient and ranged from 5 to 58 hours, [82] from 6 to 32 hours [83] and from 10 to 60 hours [84] in fasted healthy volunteers. Of significance to real-world dosing practices, the distribution of total transit times of the OROS Ò system following morning or evening dosing was different, likely related to food intake and diurnal variations in activity.…”

Stable isotope methodology for studying the performance of metoprolol Oros tablets in comparison to conventional and slow release formulations

“…The relationship between the MAT and GIIT is shown in Figure 3. (24)(25)(26). Those presently observed had a limited influence on the performance of Oros formulations since the corresponding individual MAT values (range: 5.4-15.5 h) remained higher than those obtained with the slow-release tablets (range: 2.7-4.8 h).…”

Pharmacokinetics of carbamazepine polymorphs and dihydrate in rats, related to dogs and humans

“…The 0.5-4 h peak may have been due to rapid absorption from the upper gastrointestinal (GI) tract (Wilding et al, 1991). The 4-8 h peak may be attributed to the multi-site and inhomogeneous absorption in the GI tract (Houston and Galetin, 2003).…”