Orange juice substantially reduces the bioavailability of celiprolol, but the mechanism of this interaction remains to be resolved. For example, modulation of intestinal pH and of function of transporters implicated in the absorption of celiprolol may be involved. Because of the great extent of the orange juice-celiprolol interaction and a wide use of orange juice, this interaction is likely to have clinical importance in some patients, although hemodynamic consequences were not seen in young healthy subjects.

The role of adverse drug reactions (ADRs) as a cause of hospital visits varies depending on the type of hospitals. Our aim was to determine the incidence of drug-related emergency department visits to a district hospital, and to identify the drugs and patient groups involved. All patient visits to the emergency department of a Finnish district hospital were evaluated prospectively for 6 months. The physician on duty and a clinical pharmacologist selected all possibly drug-related visits for further scrutinising. The causality assessment (drug-related or not) was judged according to WHO criteria, based on the patients' files, including laboratory and other data. Of the 7113 evaluated visits, 167 (2.3%) were ''certainly'' or ''probably'' drug-related; 102 (1.4% of all) were related to ADRs and 65 (0.9%) to intentional overdoses. The most common ADRs were gastrointestinal symptoms (nΩ17) caused by antibiotics, opioids, nonsteroidal antiin-flammatory or cytostatic drugs. The International Classification of Disease (ICD-10) codes on patients' files were insensitive to disclose ADRs. The ADR patients were older (mean age 57 years) than the intentional overdose patients (38 years; P0.001). Males predominated in the intentional overdose group (38 males, 27 females) but not in the ADR patients. The majority of intentional overdoses was caused by psychotropics. The ADRs lead to hospitalisation in a higher frequency (51%) than did the intentional overdoses (35%). In conclusion, the incidence of ''certainly'' or ''probably'' drug-related visits to the district hospital emergency room was relatively low. The ICH-10 codes on patients' files were found to be insensitive to disclose the ADRs, even when they lead to hospital admission, casting doubts on the usefulness of ICH codes alone in ADR evaluation.

Background and aimsGemfibrozil, and particularly its combination with itraconazole, greatly increases the area under the plasma concentration-time curve [AUC(0, • )] and response to the cytochrome P450 (CYP) 2C8 and 3A4 substrate repaglinide. In vitro , gemfibrozil is a more potent inhibitor of CYP2C9 than of CYP2C8. Our aim was to investigate the effects of the gemfibrozil-itraconazole combination on the pharmacokinetics and pharmacodynamics of another meglitinide analogue, nateglinide, which is metabolized by CYP2C9 and CYP3A4. MethodsIn a randomized crossover study with two phases, nine healthy subjects took 600 mg gemfibrozil and 100 mg itraconazole (first dose 200 mg) twice daily or placebo for 3 days. On day 3, they ingested a single 30-mg dose of nateglinide. Plasma nateglinide and blood glucose concentrations were measured for up to 12 h. ResultsDuring the gemfibrozil-itraconazole phase, the AUC(0, • ) and C max of nateglinide were 47% (range 23-74%; P < 0.0001) and 30% (range -8% to 104%; P = 0.0146) higher than during the placebo phase, respectively, but the t max and t 1/2 of nateglinide remained unchanged. The combination of gemfibrozil and itraconazole had no effect on the formation of the M7 metabolite of nateglinide but impaired its elimination. The blood glucose response to nateglinide was not significantly changed by coadministration of gemfibrozil and itraconazole. ConclusionsThe combination of gemfibrozil and itraconazole has only a limited influence on the pharmacokinetics of nateglinide. This is in marked contrast to the substantial effect of this combination on the pharmacokinetics of repaglinide. The findings suggest that in vivo gemfibrozil, probably due to its metabolites, is a much more potent inhibitor of CYP2C8 than of CYP2C9.