HPLC Method for Determination of Enantiomeric Purity of a Novel Respiratory Fluoroquinolone: WCK 1152.

A sensitive, simple, specific, precise, accurate and rugged method for determination of enantiomeric purity of S-(-)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-{4-amino-3,3-dimethylpiperidin-1-yl}-4-oxo-quinoline-3-carboxylic acid hydrochloride monohydrate, WCK 1152, a new drug substance has been developed. The method is based on prederivatization of analyte to diastereomer followed by RP-HPLC using endcapped C-18 stationary phase. Column was maintained at 30 degrees C. The UV/Vis detector was operated at 290 nm. Flow rate of the mobile phase was 1.25 ml/min. The method offers excellent separation of two enantiomers with resolution more than 4 and tailing factor less than 1.5. The method was validated for the quantification of R-(+)-enantiomer impurity, WCK 1153 in the bulk drug. Calibration curves showed excellent linearity over the concentration range of 0.1 to 1.5 mg/ml for WCK 1152 and 0.01 to 0.15 mg/ml for WCK 1153. Precision of the method was 1.13%. Limit of detection and limit of quantitation of the method for WCK 1152 were 0.0006 mg/ml and 0.0018 mg/ml and for WCK 1153 were 0.0007 mg/ml and 0.0021 mg/ml, respectively. Average recovery of the WCK 1153 in WCK 1152 was 94.4%. This method was employed in determining enantiomeric purity of clinical trial batches of WCK 1152.

Improved specificity of myocardial thallium-201 single-photon emission computed tomography in patients with left bundle branch block by dipyridamole.

Reduced septal uptake of thallium-201 during exercise is frequently observed in patients with left bundle branch block (LBBB) and normal coronary arteries. This may reflect normal coronary autoregulation in response to lower septal oxygen demand; thus, dipyridamole, which uniformly exploits flow reserve, would be more accurate for diagnosis of coronary artery disease (CAD). Sixteen patients with LBBB underwent exercise and dipyridamole thallium-201 single-photon emission computed tomography and coronary angiography within 3 months. Sensitivity for detection of left anterior descending CAD (greater than 50% stenosis) was 0.83 for exercise and 1.00 for dipyridamole. Specificity was 0.30 (visual) or 0.20 (quantitative analysis) for exercise and 0.80 (visual) or 0.90 (quantitative) for dipyridamole (p less than 0.05). Dipyridamole combined with quantitative analysis also improved specificity of CAD detection overall (p less than 0.01). These data demonstrate that pharmacologic vasodilation is more accurate than exercise when diagnosing CAD by myocardial perfusion scintigraphy in patients with LBBB.

Bevantolol disposition in patients with hepatic cirrhosis.

Bevantolol is a new, cardioselective beta-receptor antagonist that undergoes extensive hepatic biotransformation. To evaluate changes in the disposition of bevantolol produced by liver disease, a single 200-mg oral dose of bevantolol was administered in ten patients who had hepatic cirrhosis and to ten age-matched controls. Cirrhotic patients had a greater plasma bevantolol half-life (6.9 +/- 4.0 hr, mean +/- SD) then did patients with normal liver function (2.8 +/- 1.1 hr, P less than .01), and they also had a longer duration of significant bevantolol-induced heart rate slowing (for 12 hours after oral dose in cirrhotics versus three hours for controls). On the other hand, the peak concentration after the oral dose and the magnitude of bradycardiac effect were similar for both groups. Plasma bevantolol half-life was more variable in cirrhotic patients than in controls. Some of this variability among cirrhotics was attributable to age, which was a significant determinant of bevantolol half-life in the cirrhotic (but not in the control) patient sample. These results indicate that hepatic cirrhosis alters the disposition of bevantolol and suggest that modifications in bevantolol dose should be considered when using this drug to treat patients with liver disease.

Age-dependent lidocaine disposition in patients with acute myocardial infarction.

To evaluate age-dependent changes in lidocaine disposition in patients with acute myocardial infarction, we measured plasma concentrations of lidocaine and its metabolites monoethylglycinexylidide and glycinexylidide after discontinuation of a maintenance lidocaine infusion. Plasma lidocaine clearance was calculated by dividing the lidocaine concentration at the end of the infusion into the maintenance infusion rate. Lidocaine clearance in 35 patients was related to body weight and was reduced by heart failure. Heart failure was more common in the elderly, occurring in 15 of 27 (56%) patients over 65 years old and seven of 29 (24%) patients under 65 years old. There was a reduction in lidocaine clearance with age due, in part, to lower body weight and a higher prevalence of heart failure in the elderly. Multilinear regression analysis showed that age and weight contributed to the prediction of lidocaine plasma clearance in patients with and without heart failure. Age was a particularly important predictor of lidocaine clearance in patients with heart failure. Adjustment of lidocaine maintenance doses based on age, weight, and heart failure may help control the frequency of lidocaine adverse reactions in the elderly.

Micromorphology and histochemistry of polysaccharides in the goat mandibular salivary gland.

The micromorphology and histochemistry of mucosubstances in mandibular salivary gland of goat were studied. Encapsulated ganglia were present in the interlobular connective tissue giving nerve fibres to the ducts and blood vessels therein. The mandibular gland of goat was a mixed tubuloacinar gland possessing mucous tubules and acini, the latter capped by seromucous demilunes. The mucous secretory units contained high amounts of neutral and acidic sulfated mucosubstances. The seromucoid demilunes contained neutral and less acidic nonsulfated mucosubstances. No glycogen was found in both types of secretory cells.