Comparison of the pharmacodynamic and pharmacokinetic profiles of single and multiple doses of a commercial slow‐release metoprolol formulation with a new Oros delivery system.

Abstract

1 A new osmotic pressure mediated delivery system for metoprolol (Lopresor Oros) has been evaluated by measuring the haemodynamic effects and pharmacokinetics after single and multiple oral dosing in young healthy volunteers. 2 Similar studies have been carried out in the same group using equivalent single and multiple oral doses of the commercial slow‐release preparation (Slow Lopresor). 3 The new osmotic delivery system produces a more uniform haemodynamic response: a plateau metoprolol concentration in plasma is reached about 6 h after dosing and is maintained for 10 h.

Degradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug Release

“…1960s: the macroscopic era of polymeric drug delivery. (1) Norplant is an upper-arm-implantable polymeric drug delivery depot for contraceptive use [active pharmaceutical ingredient (API): progestin levonorgestrel]; 1 (2) Ocusert is a drug-eluting polymeric eye implant for the treatment of glaucoma or ocular hypertension (API: pilocarpine); 2 (3) Progestesert is a T-shaped polymeric IUD for contraceptive use (API: progesterone); 3 (4) Transderm Scop is a polymer-based skin-patch drug delivery system for the treatment of motion sickness (API: scopolamine); 26 (5) OROS is a polymeric capsule system for oral delivery (numerous APIs, including salbutamol, nifedipine, hydromorphone, verapamil, paliperidone, nifedipine); 2,27,28 (6) Geomatrix is a polymeric tablet system for oral delivery (API: diclofenac, molsidomine, zileuton, nisoldipine, alfuzosin hydrochloride, ropinirole, paroxetine, levodopa, and benserazide); 29,30 (7) Gliadel is an implantable polymeric disk for the treatment of glioblastoma multiforme [API: bis(2-chloroethyl)nitrosourea (BCNU)]; 31,32 (8) Vicryl is a degradable surgical suture; 34 Taxus is a polymer-coated metal drug-eluting stent for prevention of restenosis (API: antiproliferative drugs such as paclitaxel). 35,36 1980s: the microscopic era of polymeric drug delivery.…”

Polymorphic metabolism of beta‐adrenoceptor antagonists.

“…Therefore, these formulations may offer no advantage over the conventional tablets since they too must be prescribed twice daily in angina unless the oxidation phenotype is known. The new Oros preparation of metoprolol may prolong the delivery of the drug sufficiently to enable once-daily dosing in some patients (Kendall et al, 1982 matic (Cruickshank, 1983) and important doserelated changes in resting heart rate have not been observed. This is illustrated by the observation that a four-fold increase in propranolol or metoprolol dose was associated with only an additional 5-6 beats/min reduction in resting heart rate (Collste et al, 1980;Leonetti et al, 1975;Serlin et al, 1980).…”

“…Therefore, these formulations may offer no advantage over the conventional tablets since they too must be prescribed twice daily in angina unless the oxidation phenotype is known. The new Oros preparation of metoprolol may prolong the delivery of the drug sufficiently to enable once-daily dosing in some patients (Kendall et al, 1982). However, its performance in relation to oxidation phenotype needs to be assessed should it be marketed.…”

A multiple dose pharmacokinetic and pharmacodynamic evaluation of conventional and 19/285 Oros formulations of metoprolol in healthy volunteers.

“…In some cases it may be necessary to adjust both parameters to achieve the desired result. Continuous drug release at a slow rate for a prolonged period should produce steady plasma concentrations of the drug and therefore sustained action (Kendall et al, 1982). To (Kendall et al, 1980) probably as a result of reduced clearance and first-pass metabolism during chronic dosing.…”