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C H Ramsay

Publications and source records attributed to C H Ramsay.

12 recordsLinked to original sources

Redistribution of lidocaine and bupivacaine after intrathecal injection in mice.

Redistribution of lidocaine and bupivacaine was studied after intrathecal injection in mice qualitatively by whole-body autoradiography or quantitatively by determining spinal cord concentration of the drugs. The composition of the drug solutions then were changed to see if drug distribution could be altered. Changing the pH of the lidocaine solution from 7.5 to 5.0 by adding hydrochloric acid had no effect on spinal cord distribution. Simultaneous injection of bupivacaine and epinephrine increased the bupivacaine concentration in the spinal cord. By adding sucrose to a lidocaine solution, rostral spread of lidocaine was considerably less when the animals were restrained in a vertical position as compared with those injected with a plain solution. When lidocaine and bupivacaine were injected simultaneously, the spinal cord concentration was only changed to a small extent as compared with when the drugs were given separately. Whole body autoradiography revealed that both lidocaine and bupivacaine were rapidly redistributed rostrally from the lumbar area, but quantitatively the rostral redistribution is small. Whole body autoradiography also illustrated the elimination pathways from the spinal subarachnoid space. The authors conclude that alterations in the composition of the injected drug solution can affect rostral redistribution in the spinal cord tissue.

Anesthesia, Local↗

Distribution of morphine and meperidine after intrathecal administration in rat and mouse.

Morphine and meperidine distribution in the neuroaxis were studied in rats after intrathecal injection through catheters ending at the lumbar level. 14C-Morphine and 3H-meperidine were injected with pharmacologic doses of each drug. Radioactivity was measured in spinal cord segments at different times. At 14 min the segment with maximum morphine concentration (T11-12) contained 8.6 +/- 2.4 (mean +/- SD) pmol/mg, a value 215 times higher than would be observed if distribution in the body were homogeneous. The ratio between concentration in the most rostral segment (C3-4) and in the segment with maximal concentration was 0.21 +/- 0.10. At 14 min the segment with maximum meperidine concentration (T9-10) contained 161.4 +/- 33.9 pmol/mg wet tissue, a value 75 times higher than would be seen with even distribution in the body. The ratio (C3-4 vs. T9-10) was 0.10 +/- 0.04 at this time. The distribution of 14C-morphine in the whole central nervous system (CNS) was studied in mice by whole body autoradiography after intrathecal injections of 5 microliters at the L5-6 level. High levels of radioactivity were detected in the whole spinal cord and in brain regions close to the basal cisterns until 2 h after injection. At 4 h only the caudal part of the spinal cord had detectable levels of radioactivity. The per cent of the injected dose of morphine that was recovered from the spinal cord was 26.5 +/- 4.5 at 14 min, 19.9 +/- 8.8 at 44 min, and 4.5 +/- 1.7 at 179 min after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Localization of omeprazole and metabolites in the mouse.

Omeprazole is a substituted benzimidazole which blocks gastric acid secretion by inhibiting H+K+ATPase. Radioactive omeprazole was given intravenously or orally to mice, and the distribution of the drug was investigated at various intervals by scintillation counting and by autoradiography. The half-life for radioactivity in the stomach was 14 hours versus 30-36 hours in the liver, kidneys and blood. At 16 hours after the drug was given, the radioactivity in the stomach was ten times higher than that in the liver and kidneys, and 100 times that in the blood. Whole-body autoradiography showed sustained high levels of radioactivity only in the gastric mucosa. Light microscopic autoradiographic investigations of the gastric mucosa from mice killed 1 or 16 hours after the drug was given revealed radioactivity in the parietal cells. By electron microscopy of gastric mucosa from the mouse killed 16 hours after omeprazole injection the isotope label was found mainly over the secretory surface and the tubulo-vesicles. At these locations H+K+ATPase has previously been demonstrated, and it is suggested that omeprazole--or its metabolites--binds to this enzyme.

Animals↗

Distribution of terbutaline.

Whole body autoradiographic studies performed with [3H]terbutaline after intravenous and oral administration in mice revealed that the tissue and organ radioactivity was similar to or lower than the blood radioactivity with the exception of excretory organs. This can be explained by the hydrophilic nature of terbutaline and its metabolites. However, it is noteworthy that the organ (e.g. lung and heart) concentrations of unchanged terbutaline can exceed those found in serum severalfold. This was most obvious when the drug was administered via the respiratory tract and the effect became more pronounced with time after administration. It may be explained by a more rapid clearance of drug from the blood than redistribution from tissues into the blood.

Animals↗

Bacampicillin: a new orally well-absorbed derivative of ampicillin.

Bacampicillin (proposed international nonproprietary name), 1'-ethoxycarbonyloxyethyl 6-(d-alpha-aminophenylacetamido)penicillanate, is a new orally well-absorbed penicillin, highly active in vivo due to rapid transformation into ampicillin. The compound is stable in vitro at gastric pH and hydrolyzed slowly to ampicillin at neutral pH but very rapidly in the presence of biological fluids, e.g., tissue homogenates or serum. In vivo the transformation into ampicillin is so rapid that no unchanged compound could be detected in the blood after oral administration of bacampicillin to rats, dogs, and humans. On oral administration to mice, rats, and dogs, bacampicillin was found to be better absorbed than ampicillin, giving higher and earlier peak blood levels of ampicillin. The bioavailability of bacampicillin in rats and dogs was three to four times higher than that of an equimolar amount of ampicillin. On oral administration to rats, bacampicillin was found to give higher levels of ampicillin in organs such as the kidney, liver, and spleen than ampicillin itself. In "tissue cages" in rats, higher transudate levels of antibiotic were found after oral administration of bacampicillin than after ampicillin. On oral treatment of experimentally infected mice, bacampicillin was found to be more active than ampicillin.

Ampicillin↗