[Dehiscence of the superior semicircular canal: report of a case and bibliography review]. / Dehiscencia del conducto semicircular superior: presentación de un caso y revisión bibliográfica.

We present a case of deficiency of the superior semicircular canal (SSCD) in a 37 years old patient that came to us because of episodes of subjective vertigo in response to intense sounds (Tullio phenomenon). The audiometry, electronistagmography, timpanometry and stapes reflexes were normal and the fistula test was negative. The CT scan showed an absence of bone overlying the superior semicircular canal (SSC) of the right ear and the left ear was normal. When both ears were exposed to intense sounds, only the right one presented vertigo was, without nystagmus.

Pharmacokinetics of the new oral blood glucose-lowering agent (-)-2-(4-tert.-butylphenoxy)-7-(4-chlorophenyl)-heptanic acid sodium salt in mice, rats and dogs.

The pharmacokinetic behavior of the alpha-activated carbonic acid (-)-2-(4-tert.-butylphenoxy)-7-(4-chlorophenyl)-heptanic acid sodium salt ((-)-BM 13.1074-Na) was examined in ob/ob mice, rats and dogs. By applying an enantioselective HPLC-method, the in vivo stability of the administered (-)-enantiomer could be demonstrated in all tested species. After oral administration the compound was absorbed quickly and maximum plasma levels were reached within 1 h (ob/ob mice and rats) and 3 h (dogs), respectively. In dose proportionally studies in ob/ob mice, with doses of 0.25 and 1 mg/kg, a clear non proportional-increase of the plasma levels was observed. The terminal half-lives of (-)-BM 13.1074 after multiple dosing are approx. 30 h in ob/ob mice, 9 h in rats and approx. 380 h in dogs. The average effective plasma concentration in ob/ob mice is found to be 43.5 mg/l; minimal toxic concentrations are 58.8 mg/l in rats and 105.6 mg/l in dogs, respectively.

Conventional and enantioselective determination of a new blood glucose-lowering agent in biological fluids using liquid-liquid extraction and high-performance liquid chromatography.

Two analytical methods are described for the determination of 2-(4-tert.-butylphenoxy)-7-(4-chlorophenyl)heptanoic acid sodium salt (I) in animal models (beagle dog and rat). Method 1 is conventional reversed-phase high-performance liquid chromatography on an octadecylsilane column with an eluent of acetonitrile-0.02 M potassium buffer (pH 3) (65:35, v/v). Method 2 is used for the enantioselective determination of I. This method uses a chiral column (Chiralcel OJ) with an eluent of n-hexane-2-propanol (95:5, v/v) containing 3 ml/l trifluoracetic acid. The analytical procedure has a recovery of more than 90%; within-run precision of less than 5.1%, and between-run precision of less than 4.3%.

Dose proportionality studies of novel thiazolidinedione derivatives as potent antidiabetic agents in mice.

The determination of the plasma concentrations of the new oral antidiabetic agents BM 13.1246 ((+/-)-5-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)-ethoxy] benzyl]-2,4-thiazolidinedione), [sequence: see text] BM 13.1215 ((+/-)-5-[(5-methyl-2-phenyl-4-oxazolyl)-methyl-2- benzofuranyl-5-methyl]-2,4-oxazolidinedione), [sequence: see text] and BM 50.1050 ((+/-)-5[4-[2-(5-methyl-2-phenyl-4-oxazolyl)-ethoxy] naphthalyl]methyl-2,4-thiazolidinedione) [sequence: see text] in ob/ob mice plasma was performed by using liquid-liquid extraction and high-performance liquid chromatography with ultraviolet (270 nm) detection. The analytical procedures have recoveries of more than 80%, and a between-run precision of less than 4% for all analysed compounds. The pharmacokinetic behaviour, especially the dose proportionality, was investigated in ob/ob mice after repeated oral doses of 1 and 10 mg/kg, respectively. All compounds were absorbed quickly and attained maximum plasma concentrations within 2-5 h after administration. In the examined interval of dosing, an approximately proportional increase of the plasma levels for BM 13.1246 and BM 50.1050 was observed. After repeated oral doses the terminal half-lives are about 4 h for BM 13.1246, 8 h for BM 13.1215, and 6 h for BM 50.1050.

Pharmacokinetics of some new oral blood glucose-lowering agents in dogs.

The determination of the plasma concentrations of the new oral antidiabetic agents BM 17.0505 (2-(4-cyclopentylphenoxy)-7- (4-chlorphenyl)-heptanic acid), BM 13.1196 (2-(4-chlorphenyl)- heptanic acid), BM 13.1196 (2-(4-cyclopentylphenoxy)-7-(2-methoxy- phenyl)-heptanic acid: BM 13.1188 (2-(4-benzylphenoxy)-7-(2-methoxy- phenyl)-heptanic acid) and BM 13.1180 (2-(4-butylphenoxy)-5- (4-chlorphenyl)-pentanic acid) in dog plasma were performed by using liquid-liquid extraction and high-performance liquid chromatography with ultraviolet (220 nm) detection. The analytical procedures have recoveries of more than 90%, and a between-run precision of less than 5% for all analysed compounds. The pharmacokinetic behaviour, especially the dose proportionality, was investigated in dogs after a single oral dose of 5 and 50 mg/kg and repeated oral doses of 5 and 50 mg/kg, respectively. All compounds were absorbed quickly and attained maximum plasma concentrations within 1-3 h after administration. In the examined interval of dosing, a clear non proportional increase of the plasma levels was observed. After repeated oral doses the terminal half-lives are about 60-70 h (BM 17.0505), 80 h (BM 13.1196), 30 h (BM 13.1180) and 100-140 h (BM 13.1180).