Osmotic delivery systems for the beta‐adrenoceptor antagonists metoprolol and oxprenolol: design and evaluation of systems for once‐ daily administration.

1 Plasma drug concentrations, and heart rate and blood pressure responses to exercise at a predetermined load were examined in twelve hypertensive patients following single and repeated doses of oxprenolol administered once daily as oral osmotic drug delivery systems (10/170 and 16/260 oxprenolol OROS). 2 Plasma oxprenolol concentration profiles after each preparation were consistent with the criteria for sustained drug release. Levels immediately after exercise were significantly higher than those prior to exercise (P < 0.001), but differences were slight. 3 Both OROS drug forms reduced exercise heart rate for 24 h after single and repeated doses; effects were greater for 16/260 OROS than for 10/170 OROS. Significant reductions in post-exercise systolic BP were observed 24 h after drug administration and after repeated doses there was little difference between the preparations. Effects on diastolic BP after exercise were slight. 4 The relationship between plasma oxprenolol concentrations and exercise heart rates fitted an exponential mathematical model which makes allowance for inter-individual variability. No such kinetic-dynamic relationship could be defined for post-exercise systolic or diastolic BP.

Section: Discussionmentioning

confidence: 68%

Concentration‐effect relationships for oxprenolol in patients with essential hypertension.

McInnes

Brodie

1988

“…At the same times as the dogs were dosed, equal numbers of systems were placed in the in vitro release apparatus (Theeuwes et al, 1985). These systems were removed at the time the dogs were sacrificed, and assayed for residual drug content using an identical analytical procedure.…”

Section: Animal Selection and Preparationmentioning

confidence: 99%

“…These results were then compared with those obtained in the in vivo experiment. Theoretical curves for release rate or cumulative amounts released were also calculated from the known physicochemical properties of the drug, the physical dimensions of the system, and the permeability characteristics of the membrane (Theeuwes et al, 1985). In vivo and in vitro performance was evaluated against this predicted behaviour of the system.…”

Section: Animal Selection and Preparationmentioning

confidence: 99%

Evaluation of oxprenolol and metoprolol Oros systems in the dog: comparison of in vivo and in vitro drug release, and of drug absorption from duodenal and colonic infusion sites.

Jw¹,

Myrback²,

Swanson³

1985

Self Cite

1 The performance of oxprenolol and metoprolol Oros systems has been evaluated in the dog. One study compared in vivo and in vitro release from both systems over 2-14 h. The other compared the systemic availabilities of both drugs after 3 h infusion at a constant rate into the cephalic and hepatic portal veins, and into the lumen of the duodenum and colon. 2 In the in vivo release studies, Oros systems were recovered throughout the gut from the stomach to the colon. The amounts of drug remaining in the systems corresponded closely to those measured in a parallel in vitro release experiment. In vitro testing is thus a reliable indicator of in vivo system performance. 3 In the absorption studies, both metoprolol and oxprenolol were shown to be subject to substantial first-pass metabolism. Additionally, for metoprolol the data indicated a significant loss during transport from the gut lumen into the portal circulation. For both drugs the availability from the colon was equal to that from the duodenum. 4 These results provide some justification for the development of oral dosage forms with extended durations of release even for drugs which undergo significant first-pass metabolism.

“…During the development of osmoticallycontrolled drug delivery systems (Theeuwes et al, 1985) for the ,-adrenoceptor blocker oxprenolol, studies were designed to characterize absorption of this drug throughout the human gut.…”

Section: Introductionmentioning

confidence: 99%

Jejunal and ileal absorption of oxprenolol in man: influence of nutrients and digestive secretions on jejunal absorption and systemic availability.

Godbillon¹,

Vidon²,

Palma³

et al. 1987

and 2INSERM, H6pital Saint-Lazare, 107, rue du Faubourg Saint-Denis, 75010 Paris, France 1 Study I evaluated the absorption of oxprenolol in the ileum, compared to jejunum, in healthy volunteers by an intestinal perfusion technique. Around 80 mg of drug were delivered as a saline solution directly in the small bowel. 2 Samples taken 30 cm distally to the site of perfusion showed that 63% of perfused oxprenolol was absorbed in the jejunum and 48% in the ileum; the differences were significant. 3 The plasma concentration-time profiles were similar for the two perfusions. The AUC and Cmax values of free and conjugated oxprenolol for the jejunal perfusion were significantly lower than those of ileum. They showed large but consistent intersubject variations in the two treatments. 4 Study II investigated, using the same technique, the influence of nutrients and digestive secretions on jejunal absorption and systemic availability of this drug. A saline (in treatments A and B) or a nutrient (in treatment C) solution containing oxprenolol was perfused into the jejunum below a balloon either inflated (A) or deflated (B and C). 5 The disappearance rate of oxprenolol from the jejunum was unaffected by endogenous secretions. The mean amount of drug absorbed along a 30-cm jejunal segment accounted for 52 (A) and 57% (B) of the total amount perfused. The intestinal absorption rate was markedly increased in the presence of nutrients (mean amount absorbed 96% for C). 6 The change in the rate of disappearance from the intestine had no effect on the systemic availability of oxprenolol (mean AUC values 8740, 8250 and 8020 nmol I-1 h for A, B and C, respectively) or its elimination from plasma. 7 The present findings and those obtained previously by intubation and colonoscopic techniques indicate that oxprenolol is not absorbed in the stomach but is absorbed all along the small and large intestines.