Increased brain uptake and brain to blood efflux transport of 14C-GABA in spontaneously hypertensive rats.

The brain uptake and brain to blood efflux transport of (14)C-GABA were studied in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats using 20 min bilateral in situ brain perfusion in rats anesthetized using urethane. The volume of distribution (Vd) of (14)C-GABA into cerebrospinal fluid (CSF) and brain regions (cortex, diencephalon, cerebellum, and brain stem) was significantly greater in SHR than in the corresponding regions in WKY rats (p<0.05). The estimated Vd value of (14)C-GABA in CSF of SHR was 3.4 fold greater than that in WKY. Also compared to WKY, the Vd of (14)C-GABA into cerebellum and cortex of SHR was 15.3 fold and 19.4 fold greater, respectively. Although the study of blood-brain barrier (BBB) integrity using (3)H-mannitol revealed increased paracellular permeability at the brain capillaries of SHR when compared to WKY rats, this was found to be only partially responsible for the increased (14)C-GABA uptake. The study of brain to blood efflux transport of (14)C-GABA (after loading of brain with (14)C-GABA by vascular perfusion) revealed that the half-time of elimination was significantly shorter in SHR (5.35+/-0.66 min) than in WKY rats (14.83+/-1.94 min), (p<0.001). HPLC analysis revealed that GABA concentrations in brain extracts and CSF of SHR were similar to those in WKY rats (p>0.05). The faster efflux in SHR might be, at least partially, responsible to compensate for increased uptake of this neurotransmitter and to preserve the protective function of BBB towards GABA. The protective function of the BCSFB towards GABA appears to be also preserved, since systemic infusion of GABA within a wide range of administered doses (0.004-5.00 mg/kg) produced an increase in GABA CSF concentration from around 0.5 microM to only 11 microM, and the obtained pattern of CSF GABA concentrations under these conditions did not differ between SHR and WKY rats, as revealed by HPLC.

First-derivative UV spectrophotometric assay of domperidone.

Domperidone in pure form and in a number of pharmaceutical formulations (Motilium) has been determined in 0.5-N sulphuric acid by employing first-derivative at 294 nm and zero-order at 284 nm spectrophotometric modes. The results obtained by utilizing the first derivative procedure were 99.98 +/- 0.47, 101.70 +/- 0.53, 101.70 +/- 0.53 and 101.15 +/- 1.23 for the tablets, oral suspension, drops and suppositories respectively. In a similar way the results obtained for the zero order technique were 105.38 +/- 1.01, 101.70 +/- 2.57, 108.56 +/- 1.16 and 102.23 +/- 3.37 in the order. The standard addition method was adopted to evaluate the accuracy of the first derivative spectrophotometric mode.

Spectrophotometric determination of tolmetin sodium in capsule dosage form.

Two different U.V. spectrophotometric modes, zero-order and first derivative, have been applied for the quantitation of tolmetin sodium (Tolectin 200 mg) in bulk form and in its pharmaceutical formulation. Direct U.V.-measurement of aqueous solution of the drug at 325 nm exhibits significant linearity at the concentration range 0.1-1.5 mg% with a coefficient of variation (C.V.) 0.34%. The first derivative (d'A) spectrophotometric measurements at 342 nm yield results with a C.V. 0.29%. Drug assay of the capsule gives percent contents of 100.42 +/- 0.34 and 100.28 +/- 029 by adopting zero-order and d'A spectrophotometry respectively. The reproducibility and accuracy the two proposed methods have been assessed by employing standard additions technique. Accordingly the percent recoveries obtained were 99.60 +/- 0.22 and 100.16 +/- 026 for the zero order and the d'A-spectrophotometry respectively.