Going paperless: implementing an electronic laboratory notebook in a bioanalytical laboratory.

AIT Bioscience, a bioanalytical CRO, implemented a highly configurable, Oracle-based electronic laboratory notebook (ELN) from IDBS called E-WorkBook Suite (EWBS). This ELN provides a high degree of connectivity with other databases, including Watson LIMS. Significant planning and training, along with considerable design effort and template validation for dozens of laboratory workflows were required prior to EWBS being viable for either R&D or regulated work. Once implemented, EWBS greatly reduced the need for traditional quality review upon experiment completion. Numerous real-time error checks occur automatically when conducting EWBS experiments, preventing the majority of laboratory errors by pointing them out while there is still time to correct any issues. Auditing and reviewing EWBS data are very efficient, because all data are forever securely (and even remotely) accessible, provided a reviewer has appropriate credentials. Use of EWBS significantly increases both data quality and laboratory efficiency.

Interaction between ketoconazole and almotriptan in healthy volunteers.

The interaction between almotriptan, a 5-HT1B/1D agonist, and the potent CYP3A4 inhibitor ketoconazole was examined in 16 healthy volunteers. Subjects received (A) 12.5 mg almotriptan orally on Day 2 of a 3-day regimen of 400 mg ketoconazole once daily and (B) 12.5 mg almotriptan in a crossover design. Plasma and urine concentrations of almotriptan were measured by HPLC. Treatment effects on almotriptan pharmacokinetics were assessed by analysis of variance. Ketoconazole coadministration increased mean almotriptan AUC and Cmax from 312 to 490 ng h/mL and 52.6 to 84.5 ng/mL, respectively. Mean oral clearance was decreased from 40.7 to 26.2 L/h by ketoconazole, with an accompanying increase in the fraction of almotriptan excreted unchanged in the urine (40.6% to 53.3%) and a decrease in renal clearance (16.4 to 13.8 L/h). These effects were statistically significant. The effects of ketoconazole on almotriptan clearance were consistent with inhibition of the CYP3A4-mediated metabolism and a slight effect on the active tubular secretion of almotriptan.

Cardiovascular effect of almotriptan in treated hypertensive patients.

OBJECTIVE: Our objective was to investigate the cardiovascular effects of almotriptan, a 5-hydroxytryptamine 1B/1D agonist, in treated patients with hypertension. METHODS: Twenty patients with hypertension controlled by medication received the following treatments in a randomized, double-blind, crossover design: one placebo tablet, one 12.5-mg almotriptan tablet, and one 25-mg almotriptan tablet. Serial blood samples for analysis of almotriptan were obtained through 24 hours after administration. Serial measurements of supine blood pressure, 12-lead electrocardiograms, and Holter electrocardiographic recordings were also obtained. Plasma almotriptan concentrations were measured with use of a liquid chromatography-tandem mass spectrometry assay. Differences between treatments in pharmacokinetic parameters were assessed with an ANOVA model appropriate for a crossover design. Blood pressure measures and QTc intervals were analyzed for treatment effects with use of a similar model. Analyses were performed on weighted mean and maximal changes from baseline for intervals from 0 to 4 and 0 to 12 hours after administration. RESULTS: Significant linear effects of dose were observed for the maximal change in diastolic blood pressure and for the maximal and mean changes in systolic blood pressure. These effects were consistent for both the 4- and 12-hour periods after dosing. Mean changes from baseline during the interval from 0 to 4 hours were 1.59 +/- 3.88, 1.85 +/- 5.94, and 4.84 +/- 5.99 mm Hg for systolic pressure and 1.38 +/- 6.95, 6.25 +/- 9.54, and 11.0 +/- 10.6 mm Hg for diastolic pressure for placebo, 12.5 mg almotriptan, and 25 mg almotriptan, respectively. No instances of hypertensive crisis were observed. No QTc interval prolongation was observed. CONCLUSIONS: Almotriptan has effects on blood pressure in subjects with controlled hypertension that are consistent with those of other members of the pharmalogic class.