H3 Propranolol serum levels following lidocaine administration in rats with CCL4 induced liver damage.

Liver disease alters the pharmacokinetic and pharmacodynamic properties of hepatically eliminated drugs. The main factors influenced are plasma albumin levels, enzyme balance (induction & inhibition) and drug binding to tissue proteins. The influence of lidocaine on serum, heart and liver propranolol levels in Wistar rats after liver injury induced by carbon tetrachloride CCl4 0.4 ml/kg x 2/wkl, was investigated. 40 male Wistar rats were divided into four groups (I, II, III, IV; n=10), Group I animals received only propranolol (labelled + cold substance) 40 mg/kg/12 h p.o., group II propranolol plus lidocaine in a single dose of 4mg/kg s.c., group III was treated with CCl4 for 6 weeks and received propranolol x2 at the same dosage as group I, while group VI was treated with CCl4 and the same drug dosage as group II. The simultaneous administration of H3-propranolol and lidocaine increased propranolol levels in the serum and tissues. The liver in damaged animals showed an increase of propranolol level under lidocaine co-administration, probably due to CCl4 induced liver enzyme activity, resulting in a rapid propranolol metabolism or to competition between both drug protein binding sites. The increased propranolol levels in the heart after lidocaine administration were probably due to attributed to its high affinity for heart tissue. Consequently, as regards the therapeutic approach for patients with liver disease receiving propranolol their propranolol dosage should be reduced when lidocaine is co-administered.

Light induced changes in quinolone levels in rat serum and tissues.

Circadian rhythm may induce alterations of the pharmacokinetic properties of several drugs in clinical use. The aim of the study was to investigate whether lighting conditions alter the quinolone (pefloxacin) levels in serum and tissues and to determine any accumulation of the drug in the skin. Thirty male Wistar rats were divided into groups A, B, C, (n=10). The animals of group A were housed under 12h light/12h dark conditions, group B under 24h UV and group C was kept in complete darkness. All animals received 5 doses of 11mg/Kg pefloxacin every 8h for 48h.Pefloxacin levels were determined in serum, skin and femur by the inhibition zone in E.coli. in vitro. Pefloxacin concentrations in serum were increased in 24h darkness living status and decreased in 24h UV conditions as compared to group A animals. Additionally, both skin and femur pefloxacin levels were decreased under dark and UV conditions. In conclusion total light as well as total dark exposure may lead to pefloxacin pharmacokinetic changes which may have implications in the effectiveness of the drug in tissues.