Drug use evaluation of sitagliptin dosing by pharmacist versus nonpharmacist clinicians in an internal medicine department of a private physician-owned multispecialty clinic.

BACKGROUND: Sitagliptin is recommended for initial and maintenance dosing at 100 mg daily. Downward dose adjustment is recommended in patients with moderate or severe renal insufficiency. OBJECTIVE: To determine the prevalence of the potentially inappropriate initial dosing of sitagliptin based on estimated glomerular filtration rate (GFR) at baseline for pharmacist versus nonpharmacist prescribers in an internal medicine department of a private physician-owned multispecialty clinic that included a pharmacist-managed diabetes program. METHODS: This was a retrospective cross-sectional cohort analysis using data from an electronic medical record database of a private physicianowned multispecialty clinic that included a pharmacist-managed diabetes program. For patients prescribed sitagliptin between October 17, 2006, and June 5, 2008, the variables of interest were (a) the initial sitagliptin dose; (b) the GFR, calculated for each patient using the 4-point Modification of Dosing in Renal Disease (MDRD) formula at the time of initiation of sitagliptin; and (c) whether the clinician initiating the dose was a pharmacist or nonpharmacist (i.e., internal medicine physician, nurse practitioner, or physician assistant). RESULTS: Of the 290 patients prescribed sitagliptin for the first time between October 17, 2006, and June 5, 2008, 35 (12.1%) received a potentially inappropriate initial dose according to product labeling regarding renal function; 21 were over-dosed and 14 were under-dosed. Potentially inappropriate dosing occurred in 1 of 158 patients (0.6%) who had initial dosing prescribed by a pharmacist compared with 34 of 132 patients (25.8%) for nonpharmacists (P < 0.001, Fisher's exact test). CONCLUSION: Potentially inappropriate initial dosing of sitagliptin based on assessment of renal function was more likely to occur with nonpharmacist prescribers than with a pharmacist prescriber.

Lens thickness of Indian eyes: impact of isolated lens opacity, age, axial length, and influence on anterior chamber depth.

PURPOSE: To report relationship of age group and axial length (AL) category to lens thickness values in eyes with a clear lens or different types of isolated cataract (nuclear, cortical, and posterior subcapsular (PSC)). Further, we evaluated lens thickness values on anterior chamber depth (ACD) in these eyes. DESIGN: Observational clinic-based study.MethodsAn observational study of 1442 eyes of 1442 individuals (816 eyes with isolated cataract and 626 eyes with clear lens) of those above 25 years of age was evaluated. AL and lens thickness were performed with an A-scan ultrasound after dilatation of the pupil, and manual optical pachymetry was used to measure ACD after dilatation of the pupil. MAIN OUTCOME MEASURES: Lens thickness. RESULTS: Multiple regression analysis revealed that with each decade of advancement in age, the lens thickness increased by 0.155 mm (P<0.001). The difference in lens thickness after adjusting for age group and AL category was less in cortical cataract by -0.25 mm (P<0.001) and PSC by -0.29 mm (P<0.001); With advancement in AL category, lens thickness decreased by 0.004 mm (P<0.001). After adjusting for all the parameters/variables, regression analysis revealed that as lens thickness increased, there was a significant decrease in ACD (mean -0.44 mm; P<0.001). CONCLUSIONS: Lens thickness was significantly greater in clear lenses when compared with isolated cataracts-greatest with nuclear cataract and least with PSC. Age group and AL category had a significant impact on the lens thickness of both cataract and clear lens. A significant decrease in ACD was found with the increase in lens thickness.

The effects of a novel sulphidopeptide leukotriene antagonist, BAY x7195, against elicited bronchoconstriction in the anaesthetized guinea-pig.

1. The novel leukotriene antagonist Bay x7195, has been evaluated against bronchoconstriction induced by leukotriene D4 (LTD4), the thromboxane A2 (TXA2) mimetic U46619, histamine and antigen, in the guinea-pig in vivo by use of a modified Konzett-Rössler preparation. 2. LTD4, given intravenously (i.v.) at 1 or 3 microg kg(-1) in the presence of indomethacin and sotalol, caused a 50-70% maximal bronchoconstriction in most animals. 3. BAY x7195, given i.v., orally (p.o.), by aerosol or dry powder insufflation, in lactose, reduced LTD4-induced bronchoconstriction dose-dependently. The approximate ID50 values were 83 microg kg(-1), 3 mg kg(-1), 0.0003% w/v for 20 breaths and 20 microg respectively. 4. The action of BAY x7195 (10 mg kg(-1), p.o.) was long lasting, causing significant inhibition of the LTD4-induced response (88% reduction) 8 h after dosing. 5. When given intravenously, in the presence of selected antagonists, BAY x7195 caused a dose-related reduction in the antigen-induced response, with an approximate ID50 of 2 mg kg(-1). 6. At 3 mg kg(-1), i.v., a dose which abolished the response to LTD4, BAY x7195 had no effect on U46619- or histamine-induced bronchoconstriction. 7. BAY x7195 is a potent, selective and long acting antagonist of LTD4-induced bronchoconstriction, in an anaesthetized, ventilated guinea-pig model. It is therefore worthy of clinical evaluation in diseases believed to involve the sulphidopeptide leukotrienes, such as asthma.

Inhibition of antigen-induced contraction of guinea-pig airways by a leukotriene synthesis inhibitor, BAY x1005.

BAY x1005 ((R)-2-[4-quinolin-2-yl-methoxy)phenyl]-2-cyclopentyl acetic acid), an inhibitor of leukotriene synthesis, was evaluated, both in vitro and in vivo, for inhibition of antigen-induced airway contraction in the sensitised guinea-pig. Antigen (ovalbumin 0.001-10 micrograms/ml) challenge of tracheae in the presence of pyrilamine and indomethacin induced contractile responses which were inhibited by BAY x1005 with an IC50 value of 0.36 (0.2-0.8) microM. Using the same test system BAY x1005 (1 microM), ICI D2138 (0.3 microM) or AA 861 (1 microM) had similar inhibitory activities, whereas MK 886, MK 591, and Zileuton (A64077) all tested at 1 microM and REV 5901 (10 microM) had no significant effect. Using tracheae from non-sensitised (control) guinea-pigs the calcium ionophore A23187 (1 microM) induced a maximal contraction which was significantly inhibited by BAY x1005 at 1 microM, whereas MK 886 was only active at 3 microM. BAY x1005 tested at 10 microM and 3 microM had no effect against leukotriene D4- or KCl-induced contractions of guinea-pig tracheae respectively. In the anaesthetised ovalbumin sensitised guinea-pig BAY x1005 caused a dose-related inhibition of ovalbumin-induced bronchoconstriction, with approximate ID50 values of 0.85 mg/kg i.v. and 6.3 mg/kg p.o. In the same model MK 886, MK 591, AA 861 and ICI D2138 each given at 10 mg/kg p.o. had no significant inhibitory activity against antigen challenge. Six hours after administration BAY x1005 (10 mg/kg p.o.) was still effective against the antigen-induced response.(ABSTRACT TRUNCATED AT 250 WORDS)

BAY u3405 an antagonist of thromboxane A2- and prostaglandin D2-induced bronchoconstriction in the guinea-pig.

1. The novel thromboxane (TX) antagonist, BAY u3405, has been evaluated against bronchoconstriction induced by the TXA2 mimetic U-46619, prostaglandin D2 (PGD2), 5-hydroxytryptamine (5-HT), leukotriene D4 (LTD4) and histamine in the guinea-pig in vivo by use of a modification of the model described by Konzett & Rössler. 2. When given intravenously (i.v.) at 30 or 100 micrograms kg-1, U-46619 caused 80% maximal bronchoconstriction in most animals. In contrast, PGD2 caused a smaller 40%-50% maximal bronchoconstriction at the highest dose tested (300 micrograms kg-1, i.v.). 3. BAY u3405, given intravenously, orally (p.o.) or by aerosol antagonized U-46619-induced bronchoconstriction in a dose-related manner. The approximate ID50 values were 600 micrograms kg-1, i.v., 1.7 mg kg-1 p.o. and 0.1% w/v 20 breaths by aerosol. 4. BAY u3405 had similar inhibitory activities against U-46619-induced bronchoconstriction and hypertension suggesting that it had no preferential activity on the airways. 5. When given intravenously BAY u3405 antagonized the bronchoconstrictor effect of intravenous PGD2 with ID50 values between 30-100 micrograms kg-1. 6. The action of BAY u3405 (10 mg kg-1, p.o.) was long lasting, causing significant inhibition of U-46619-induced bronchoconstriction 7 h after dosing. 7. At 1 mg kg-1, i.v., a dose that abolished the response to U-46619 and PGD2, BAY u3405 had no effect on histamine-, 5-HT- or LTD4-induced bronchoconstriction. 8. BAY u3405 potently and selectively antagonized U-46619- or PGD2-induced bronchoconstriction in the Konzett-Rössler model of guinea-pig lung function. It should therefore prove to be a useful tool for defining the role of TXA2- and PGD2 in airway diseases such as asthma.

Evidence for histamine and 5-hydroxytryptamine like effects of MK-212 on guinea pig ileum, taenia coli and rat fundus strip.

MK-212 (1 x 10(-7)M -- 1 x 10(-5)M) produced dose-dependent contractions of guinea pig ileum, taenia coil and rat fundus strip. The responses to MK-212 in all three preparations were blocked competitively by cyproheptadine (1 x 10(-8)M) a 5-HT receptor antagonist. Mepyramine (1 x 10(-8)M)-H1 receptor antagonist also inhibited competitively the responses of guinea pig ileum and taenia coli to MK-212. However, it failed to block significantly the responses of rat fundus strip to MK-212. Metiamide (1 x 10(-6)M), propranolol (1 x 10(-6)M) or atropine (1 x 10(-6)M) did not produce any significant effects on MK-212 induced contractile responses of guinea pig ileum, taenia coli and rat fundus strip. Our findings suggest that MK-212 produces both 5-HT as well as histamine like effects on the guinea-pig ileum, taenia coli and rat fundus strip.