ABSTRACT:The delivery of clarithromycin (CRL) to its site of action in bronchial/alveolar epithelial cells (EC), bronchial epithelial lining fluid (ELF), and bronchoalveolar lavage cells (BALC) may be influenced by CYP3A4 and the drug transporters, ATP-binding cassette (ABC) B1 and ABCC2 and organic anion-transporting polypeptides (OATPs), which can be modulated and/or up-regulated via the nuclear pregnane X receptor (PXR) by rifampicin (RIF). Therefore, we evaluated the disposition and pulmonary distribution of CLR (7.5 mg/kg b.i.d., 21 days) and expression of ABCB1, ABCC2, OATP1A2, and OATP2B1 in EC and BALC before and after comedication of RIF (10 mg/kg b.i.d., 11 days) in nine healthy foals (41-61 days, 115-159 kg) in which the genetic homology of drug transporters is close to that of their human analogs. After RIF comedication, relative bioavailability of CLR decreased by more than 90%. Concentrations in plasma (29.8 ؎ 26.3 versus 462 ؎ 368 ng/ml), ELF (0.69 ؎ 0.66 versus 9.49 ؎ 6.12 g/ml), and BALC (10.2 ؎ 10.2 g/ml 264 ؎ 375 g/ml; all P < 0.05) were lowered drastically, whereas levels of the metabolite 14-hydroxyclarithromycin were not elevated despite higher 4␤-hydroxycholesterol/cholesterol plasma concentration ratio, a surrogate for CYP3A4 induction. In the presence of CLR, ABCC2 and PXR mRNA contents were significantly and coordinately (r 2 ‫؍‬ 0.664, P < 0.001) reduced in BALC after RIF. In EC, mRNA expression of OATP1A2 increased but that of OATP2B1 decreased (both P < 0.05). RIF interrupts oral absorption and decreases CRL plasma levels below the minimal inhibitory concentration for eradication of Rhodococcus equi. Evidence that RIF influences the cellular uptake of CLR in bronchial cells and the PXR expression in BALC in the presence of high CLR concentrations exists.

Background Drug-related problems (DRPs) endanger geriatric patients' safety. Especially a follow-up treatment with increased number of care transitions is a critical time for patients. Objective This study aimed at optimising medication therapy and the transfer of medication-related information to ambulatory care in geriatric rehabilitation patients. Setting German geriatric rehabilitation centre (GRC). Method A prospective, controlled intervention study was performed. Patients in the control group (CG) received standard care, those in the intervention group (IG) an additional dual pharmaceutical intervention: (i) medication review to optimise in-hospital medication and (ii) improvement of discharge letters for optimising transfer of medication-related information. Main outcome measure (i) Number of patients with at least one DRP at discharge and (ii) predefined quality criteria for the discharge letters. Results 150 patients were enrolled in CG and 163 in IG. (i) At discharge, 126 (84%) patients in the CG were affected by at least one DRP. In the IG, the number of affected patients decreased to 64 (39%, P < 0.05). (ii) In comparison to discharge letters in the CG, predefined quality criteria were improved in the IG. Following differences were measured (CG vs. IG, each P < 0.05): active ingredient indicated (60 vs. 99%), brand name indicated (60 vs. 96%), explanation of medication changes (47 vs. 68%), visualisation of explanations next to the discharge medication (26 vs. 91%) and recommended therapy duration for short-term medications (49 vs. 84%). Conclusion DRPs and incomplete discharge letters affected many patients. The dual intervention improved in-hospital medication therapy and optimised the transfer of medication-related information.

Background Pharmacist-led medication reviews have shown to prevent drug-related problems (DRPs). So far, data is rare about the implementation in routine care, the conditions for intensifying this service and the practical skills of community pharmacists to perform medication reviews. Objective To assess the current status of medication review implementation in German community pharmacies and the performance of identifying DRPs in a ficticious patient example. Setting German community pharmacies. Method An online survey was conducted from July to September 2015 including questions about medication reviews currently performed in routine care of community pharmacies and hidden DRPs in a ficticious patient example. Pharmacists were invited via newsletters from three local chambers of pharmacists. Main outcome measure (i) Frequency, conditions for implementation, and criteria of medication reviews currently being performed in routine care, (ii) requested further information to perform medication reviews, and (iii) proportion of pharmacists who identify DRPs in the patient example. Results A total of 143 community pharmacists completed the questionnaire. (i) One hundred and twenty-seven respondents (89 %) reported reviewing the medication regularly in routine care, whereas 56 (39 %) stated that they performed medication reviews between one and five times monthly. For 124 pharmacists (87 %), remuneration would be a necessary condition for performing medication reviews more frequently. When reviewing the medication, 112 (78 %) of the pharmacists considered the criterion 'drug-drug interactions' and 107 (75 %) reviewed the criterion 'correct dosage'. One of the least reviewed criteria was 'effectiveness of medication' [22 (16 %)]. (ii) According to the participants, laboratory values should be available in the community pharmacy, since 87/143 (61 %) would appreciate the GFR and the HbA1c level. Twenty-two of 54 respondents (41 %) would appreciate further administration instructions and 5 of 54 (15 %) think they would benefit from information about the recommended duration of drug use. (iii) Depending on the category, 4 (3 %) to 49 (34 %) of all 143 pharmacists identified the hidden DRP in the patient example. Conclusion German community pharmacists reported reviewing the medication of their patients regularly; however, most of the respondents review the medication very rarely in routine care. Consequently, their practical performance needs to be improved.

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