Single doses of norfloxacin (200, 400, 800, 1,200, and 1,600 mg) or placebo were administered orally at weekly intervals to 14 healthy male volunteers in a double-blind study. Norfloxacin was measured in serum and urine by high-pressure liquid chromatography with UV detection. The concentrations of this drug in serum peaked 1 to 2 h after each dose; the mean peak values for increasing doses were 0.75, 1.58, 2.41, 3.15, and 3.87 micrograms/ml. Mean area under the serum concentration-time curves for the first 12 h after each dose were 3.56, 6.26, 11.4, 16.1, and 19.7 micrograms . h/ml, respectively. The elimination half-life of norfloxacin was about 7 h and was similar for all doses. The concentrations of the drug in urine also peaked 1 to 2 h after dosage; mean peak values for increasing doses were 200, 478, 697, 992, and 1,045 micrograms/ml. Renal clearances approximated 285 ml/min. About 30% of each dose was excreted into urine as unmetabolized norfloxacin. Crystals of the drug were occasionally observed during microscopic examination of freshly voided urine collected after the 1,200- and 1,600-mg doses. Crystalluria was not encountered at lower doses.

1 Single oral 20 mg doses of the HMG-CoA reductase inhibitors pravastatin and lovastatin, with and without concomitant propranolol (40 mg twice daily), were administered to 16 healthy male subjects participating in a randomized, four-way crossover study. 2 Serum concentrations of total and active inhibitors were measured by bioassay and concentrations of pravastatin, two pravastatin metabolites and lovastatin acid were measured by gas chromatography/mass spectrometry. 3 Coadministration of propranolol with pravastatin reduced the mean area under the serum concentration-time curve (AUC) of total inhibitors by 23%, of active inhibitors by 20% and of pravastatin by 16%. 4 Coadministration of propranolol with lovastatin also resulted in decreases in the mean serum AUC of total inhibitors by 18%, of active inhibitors by 12% and of lovastatin acid by 13%. 5 These decreases in systemic drug concentrations may reflect enhanced drug first-pass hepatic clearance in the presence of propranolol. 6 The clinical significance of these changes is likely to be small.

A high-performance liquid chromatographic method for the analysis of norfloxacin [1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid], a new nalidixic acid analog, in human serum and urine is described. A statistical evaluation of the assay data showed acceptable accuracy and precision for 0.1 to 10.0 ,ug of MK-366 per ml of serum and for 1.0 to 500 ,ug of MK-366 per ml of urine. MK-366 was extracted from serum and urine at pH 7.5 with methylene chloride and back-extracted with sodium hydroxide solution. Chromatography was performed on an anion-exchange column with acetonitrilephosphate buffer as the mobile phase; UV absorbance was monitored at 273 nm. The method was used to measure MK-366 in clinical specimens.boxylic acid] is a new broad-spectrum antibacterial agent that is structurally related to nalidixic acid (Fig. 1). MK-366 exhibits greater antibacterial activity against both gram-positive and gram-negative bacteria than other nalidixic acid analogs and exhibits greater activity against Pseudomonas aeruginosa than gentamicin (1,2 Extraction of samples. Serum (1 ml) or urine (200 pul) was thoroughly mixed with 100 p.l of 0.05 N NaOH (containing standards preparing the standard curve) in a 40-ml glass extraction tube. Methylene chloride (11 ml) and 0.5 M sodium phosphate buffer (0.5 ml, pH 7.5) were then added, and the tubes were gently shaken for 10 min on a mechanical shaker. After phase separation by centrifugation at 1,500 x g for 5 min, 10 ml of the methylene chloride layer was transferred to a second 40-ml extraction tube. Fresh methylene chloride (11 ml) was added to the first extraction tube, and a second extraction was performed; 10 ml of the second extract was pooled with the first organic phase.

Clinical Pharmacology & Therapeutics (1999) 65, 132–132; doi:

1The pharmacokinetic parameters of morphine were determined in a crossover fashion following 4 days pretreatment with cimetidine, 300 mg every 6 h, or placebo. 2 Cimetidine had no apparent effect on the mean morphine plasma clearance, volume of distribution, AUC or half-life (P > 0.05; power > 0.80). 3 Cimetidine had no apparent effect on the magnitude or duration of morphine induced miosis. 4 The absence of a demonstrable effect on the pharmacokinetics of a drug with a high extraction ratio such as morphine suggests that cimetidine did not significantly reduce hepatic blood flow in ambulant normal volunteers.