In vivo evaluation of a new sustained-release formulation of morphine.

The pharmacokinetics of a novel sustained-release oral formulation of morphine have been evaluated. The formulation consisted of tablets containing a morphine-EudragitL complex (MEC) which had shown good sustained-release properties in previous in vitro dissolution studies. MEC tablets were administered orally to beagle dogs and the morphine plasma levels and pharmacokinetic parameters obtained were compared with those obtained with MST Continus, a commercially available sustained release form of morphine. Blood samples were withdrawn up to 12 h after dosing and plasma morphine concentrations were determined by HPLC with electrochemical detection. Both formulations presented a relatively rapid absorption of morphine with similar values of Cmax (MST: 53 ng/ml; MEC: 50 ng/ml) and Tmax (MST: 86 min; MEC: 88 min), and prolonged morphine plasma levels. Mean plasma morphine concentrations were higher for the MEC tablets than for MST tablets during the terminal phase of the corresponding curves and the mean AUC(0-12h) for MEC tablets was 138% of that obtained with MST tablets. Our findings indicate that MEC tablets can produce prolonged plasma levels of morphine and could be an alternative to commercially available morphine sustained-release forms.

Pharmacokinetic interaction between efavirenz and ketoconazole in rats.

1. It is well known that efavirenz and ketoconazole act as an inducer and inhibitor of CYP3A4, respectively. As a result of these actions, co-administration of these drugs may result in changes in the pharmacokinetic parameters of one or both of them. 2. Duodenum-cannulated rats have been used to compare the effect of intraduodenal (KC(i.d.)) and intravenous administration of ketoconazole (KC(i.v.)) on the pharmacokinetics of efavirenz after intraduodenal administration, as well as the potential effect of efavirenz as a CYP450 inducer on ketoconazole pharmacokinetic profile. 3. While KC(i.v.) did not show any significant effect on efavirenz pharmacokinetic profile, KC(i.d.) increased significantly (p < 0.05) the peak concentration (C(max)) and the area under the plasma concentration-time curve (AUC) of efavirenz by 25.5% and 44.5%, respectively. In addition, the time necessary to reach peak concentration (T(max)) increased markedly by 71%. However, the mean total clearance (CL/F) of efavirenz was significantly decreased by 45%. Efavirenz did not produce any alteration in ketoconazole pharmacokinetics. 4. These findings suggest that when the treatment starts with enteral administration of ketoconazole, the inhibitor effect on CYP450 prevails over the inducer effect of efavirenz.

Antibiotic prophylaxis for percutaneous endoscopic gastrostomy for non-malignant conditions: a double-blind prospective randomized controlled trial.

BACKGROUND: The use of antibiotic prophylaxis prior to percutaneous endoscopic gastrostomy insertion has been encouraged following development of guidelines by a number of professional societies within the past few years. However, not all evidence supports routine prophylaxis, particularly in patients with 'benign' disease indications for percutaneous endoscopic gastrostomy insertion. AIM: To identify whether prophylactic antibiotic usage is beneficial in patients undergoing percutaneous endoscopic gastrostomy insertion without malignant disease. METHODS: Adult patients without malignant disease who were referred for percutaneous endoscopic gastrostomy insertion at our unit were assessed for participation in this prospective, double-blind, randomized controlled study. Patients were randomized to receive either placebo or 2.2 g co-amoxiclav (or 2 g cefotaxime if penicillin-allergic) at time of percutaneous endoscopic gastrostomy insertion. Clinical endpoints studies were percutaneous endoscopic gastrostomy site or systemic infection and death within 7 days of percutaneous endoscopic gastrostomy insertion. Results : Ninety-nine patients completed the study (51 antibiotics, 48 placebo). Outcomes in the antibiotic and placebo groups respectively were: percutaneous endoscopic gastrostomy site infection, 11% vs. 47% (P < 0.01); systemic infection, 16% vs. 38% (P < 0.05); and death, 8% vs. 15% (P = 0.5). CONCLUSIONS: Antibiotic prophylaxis prior to percutaneous endoscopic gastrostomy insertion reduces both percutaneous endoscopic gastrostomy site and systemic infections in patients without malignant disease.