Effects of a multifaceted intervention in psychogeriatric patients: one-year prospective study.

OBJECTIVES: The aetiology of behavioural and psychological symptoms (BPSD) could be related to inadequate treatment in patients with dementia. The aim of this study was to determine how a multifaceted intervention based on a medication review and multidisciplinary follow-up could improve treatment and minimise risk in these patients. METHODS: A prospective interventional study was undertaken between July 2015 and July 2016 of patients with dementia admitted to control BPSD. Patients with previous psychiatric illness or palliative care were excluded. Prescription information was obtained from Aegerus and the Catalonia clinical record HC3. The intervention was conducted by a multidisciplinary team. The Medication Appropriateness Index (MAI) was used to assess the intervention. RESULTS: 65 patients (60% women, mean age 84.9±6.7 years) with mild-moderate cognitive impairment (mean 4.5±1.8), moderate-severe functional dependence (mean 43.8±23.9) and a high prevalence of geriatric syndromes and comorbidity were included in the study. 87.7% of the patients were taking ≥5 drugs (mean 9.0±3.1) and 38.5% were taking ≥10. Patients presented with BPSD values of 1.9±0.8 at admission. Common symptoms prompting admission were agitation (47.7%) and irritability (43.1%). A total of 175 drug-related problems (DRPs) were detected (2.97 per patient). Significant differences (p<0.001) were found between the MAI score at admission (4±4.6) and post-intervention (0.5±2.6). Most prevalent MAI criteria were related to interactions (40%), dosage (38.5%) and duplication (26.2%). 55 patients (84.6%) were taking anticholinergic drugs at admission (2.6±1.2 anticholinergic drugs per patient), and the post-intervention reduction was significant (p<0.016). CONCLUSIONS: The balance between effective treatment and safety is complex in these patients. Medication review in interdisciplinary teams is an essential component to optimise interventions and assessment of safety.

Bioequivalence Study of Two Long-Acting Formulations of Oxytetracycline Following Intramuscular Administration in Bovines.

The aim of this study was to evaluate the bioequivalence of two commercial long-acting formulations based on oxytetracycline (OTC) hydrochloride between the reference formulation (Terramycin LA, Pfizer) and a test formulation (Cyamicin LA, Fort Dodge Saude Animal). Both formulations were administered in a single intramuscular route at a dose of 20 mg OTC/kg of body weight in clinically healthy bovines. The study was carried out according to a one-period parallel design. Plasma samples were analyzed by high-pressure liquid chromatography. The limit of quantitation was 0.050 µg/mL with an accuracy of 101.67% with a coefficient of variation of 13.15%. Analysis of variance and 90% confidence interval tests were used to compare the bioavailability parameters (maximum plasma concentration, C max, and the area under the concentration-versus-time curve extrapolated to infinity, AUC0-∞) of both products. In the case of the time to maximum concentration (T max), non-parametric tests based on Wilcoxon's signed rank test were preferred. The comparison of the mean AUC0-∞ values did not reveal any significant differences (311.40 ± 93.05 µg h/mL and 287.71 ± 45.31 µg h/mL, respectively). The results were similar for the T max (3.58 ± 0.90 h versus 3.42 ± 0.51 h). However, when comparing the mean C max some significant differences were found (8.73 ± 3.66 µg/mL and 10.43 ± 3.84 µg/mL, respectively). The 90% confidence intervals for the ratio of AUC0-∞ and T max values for the reference and test product are within the interval 80-125%, but the 90% confidence intervals for the ratio of C max falls outside the proposed interval. It was concluded that C max of test product are not within the 20% of those of the reference, thus suggesting that test OTC is not bioequivalent to the reference formulation.

Sunitinib tissue distribution changes after coadministration with ketoconazole in mice.

Sunitinib is a multitargeted tyrosine kinase inhibitor approved for gastrointestinal stromal tumor (GIST), advanced renal cell carcinoma (RCC) and pancreatic neuroendocrine tumors. It is metabolized via CYP3A4 and has low brain penetration due to efflux transporters ABCB1B and ABCG2. We studied the interaction with ketoconazole (50 mg/kg), antifungal drug which shares metabolic pathways and efflux transporters, in ICR female mice after oral coadministration (30 min apart) of 60 mg/kg sunitinib (study group) versus sunitinib alone (control group). Plasma, liver, kidney and brain sunitinib concentrations were measured by HPLC at 2, 5, 10, 20, 40 min, 1, 2, 4, 6, 12 h post-sunitinib administration, and non-compartmental pharmacokinetic parameters estimated. In plasma, ketoconazole coadministration increased plasma maximum concentration (C MAX) 60 %, delayed time to C MAX (T MAX); 1.6-fold greater area under the curve AUC0→∞ (p < 0.001); lower apparent steady-state volume of distribution (V SS/F) and oral clearance (Cl/F) 40 and 61 %, respectively; and shorter elimination half-life (t 1/2). Sunitinib exhibited extensive tissue distribution which increased after ketoconazole coadministration: total area under the curve (AUC0→∞) increased 1.8-, 2.8- and 1.2-fold in kidney, liver and brain, respectively (all p < 0.001). Sunitinib presented high tissue-to-plasma AUC0→∞ ratio in liver (17.8 ± 1.2), kidney (14.6 ± 1.52) and brain (2.25 ± 0.18) which was modified after coadministration: AUC0→∞ ratio increased in liver (31.4 ± 4.7; p < 0.001), kidney (17.1 ± 2.2; p > 0.05) and decreased in brain (1.70 ± 0.23, p > 0.05). The results showed a significant ketoconazole-sunitinib interaction that affected plasma, tissue pharmacokinetics and tissue uptake mechanisms. The study portrays the risk to increase toxicity and potential clinical translatability to treat tumors in tissues.