Adjuvant arthritis, as a model for investigating rheumatoid arthritis (RA), is characterized by reduced plasma albumin levels and interferes with drug binding in the plasma and tissues (liver and bone). Ampicillin interacts with non-steroidal anti-inflammatory drugs (NSAIDs) due to the acidic pk(a). The aim of this study was to investigate in vitro the concentrations of ampicillin in the serum, femur, mandible and liver proteins following the co-administration of ketoprofen, flurbiprofen, ibuprofen, oxyphenbutazone and ASA in adjuvant arthritis versus healthy control rats. Ampicillin binding was found to be reduced in the serum of arthritic rats, and ampicillin binding to serum proteins was also reduced under the influence of NSAIDs in the control animals. Differences in ampicillin binding were observed in the various tissues due to the effect of adjuvant arthritis as well as that due to the co-administration of NSAIDs. In conclusion, this in vitro study may provide a plausible explanation for the ampicillin-NSAIDs interaction and such a finding may be of therapeutic significance in the treatment of painful arthritic disease such as RA.
The co-administration of lidocaine and propranolol leads to significant drug-drug interactions. Beta-blockers decrease liver perfusion and inhibit the activity of hepatic microsomal lidocaine metabolizing enzymes of the P450_2D subfamily. Hence, there is a resulting reduction in the hepatic breakdown of lidocaine and an increase in its serum concentrations. In this study the ability of propranolol to displace lidocaine from its binding sites in liver tissue has been examined through an in vitro model. Rat liver slices were incubated together with propranolol and/or lidocaine in human serum and the percentage of the bound fraction of lidocaine in the experimental mixture was assessed. The present results indicate that propranolol significantly decreases the binding process of lidocaine in liver tissue. This effect develops only when blood is used as incubation medium and the incubation period lasts 60 min. In conclusion, propranolol can displace lidocaine from liver proteins and therefore the co-administration of the two drugs may increase the free fraction of lidocaine excreted by the liver. However, this result arises from an in virro model and thus further investigation is needed.
Lidocaine is a local anaesthetic widely used in regional and epidural anaesthesia. Clonidine a alpha2-adrenergic agonist is an antihypertensive agent, regulating the production of catecholamines (epinephrine and norepinephrine) and added to local anesthetic infusions in order to improve postoperative analgesia. The aim of the study was to investigate the influence of clonidine co-administration on the binding of 14C lidocaine to rat serum and heart tissue protein as well as its pharmacodynamic effects in the heart. Four groups of Wistar rats (n=7) were used; Groups I and II received 4 mg/kg lidocaine i.m. Groups III and IV received lidocaine and 1 microg/kg clonidine i.m. In group I and III fifteen minutes and in groups II and IV thirty minutes after the initial treatment, ultrasound examination of heart function (heart rate, diameter of left ventricle in systole and diastole, ejection fraction) was performed. The animals were then sacrificed in all groups. Lidocaine free fraction in serum and heart was evaluated via ultrafiltration. The kinetics of lidocaine was altered by clonidine co-administration probably by mechanisms related to protein binding alterations. However, the pharmacokinetic interactions were not accompanied by changes of pharmacodynamic parameters including those of heart function as measured by echocardiography.
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