Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A mexiletine (Mexitil, MEX) administration schedule was established by simulation, in order to maintain MEX at therapeutic levels in plasma during the transition from parenteral to slow-release MEX (SR MEX) administration. This protocol was made valid in 6 patients with acute myocardial infarction (AMI) admitted to a coronary care unit, 24 h after the onset of pain. From both the i.v. and oral plasma level data, the pharmacokinetic parameter alterations of MEX and its hydroxymethylmexiletine metabolite (OH MEX) were evaluated over a week's period. The results presented here demonstrate that a twice daily oral SR MEX administration, starting at the end of MEX infusion, maintains the therapeutic concentrations of MEX (750-2000 ng/ml) previously achieved by infusion therapy (at 48 h, end of infusion, mean +/- SD = 1393 +/- 325 ng/ml; at 60 h, mean +/- SD = 1434 +/- 376 ng/ml; at 96 h, mean +/- SD = 1423 +/- 367 ng/ml. No evidence of either clinical side-effects or malignant arrhythmias was observed. MEX and OH MEX pharmacokinetic parameters were estimated by fitting the i.v. infusion data (phase I) and the oral data after the last SR MEX administration (phase II)beta to a linear compartment model. The terminal half-life t1/2 MEX was longer in phase I than in phase II (28.4 +/- 12.1 h (betaI) versus 14.06 +/- 4.47 h (II); p less than 0.01). This prolonged t1/2 MEX was probably due to a decrease of total plasma clearance Cl MEX (3.723 +/- 1.534 ml.kg-1min-1 (I) versus 5.031 +/- 1.28 ml.kg-1min-1 (II).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mexiletine in acute myocardial infarction. Simulation of a theoretical protocol and validation in six patients. 281 79

In the present study, we investigated whether dynamic and static allodynia would be developed in the affected dermatome in murine models of herpetic pain and postherpetic neuralgia and pharmacologically characterized the allodynia. Inoculation with herpes simplex virus type-1 on the femur induced skin lesions in the dermatome including the plantar region of the hind paw from day 5 to day 21 after inoculation. Dynamic allodynia became apparent in the hind paw from day 3 to at least day 42. Static allodynia was not obvious during the stage of herpetic pain and gradually increased after the lesion healing. Mexiletine hydrochloride (30 mg/kg, p.o.) and ketamine hydrochloride (50 mg/kg, i.p.) produced a moderate attenuation of static but not dynamic allodynia. Diclofenac sodium (50 mg/kg, i.p.) did not affect both static and dynamic allodynia. Gabapentin (30 mg/kg, p.o.) markedly inhibited both static and dynamic allodynia. Developmental and pharmacological differences between static and dynamic allodynia suggest that independent mechanisms are responsible for dynamic and static allodynia. This murine model may be useful for the study of the mechanisms of dynamic allodynia of herpetic pain or postherpetic neuralgia and the development of new analgesics effective against the dynamic allodynia.
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PMID:Pharmacological differences between static and dynamic allodynia in mice with herpetic or postherpetic pain. 1898 31