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Biomedical subjects

V Jamieson

Publications and source records attributed to V Jamieson.

11 recordsLinked to original sources
PubMed1999

Adjustment of carbamazepine dose to offset the effects of the interaction with remacemide hydrochloride in a double-blind, multicentre, add-on drug trial (CR2237) in refractory epilepsy.

PURPOSE: The efficacy of remacemide hydrochloride (REM) as an antiepileptic drug (AED) was tested in a double-blind, add-on trial in patients with refractory epilepsy. Concurrent drugs included carbamazepine (CBZ). The interfering effects of the pharmacokinetic interaction between REM and CBZ were offset by the monitoring of plasma CBZ concentration and the appropriate reduction of CBZ dose by an unblinded observer. METHODS: Patients taking CBZ entered a 4-week run-in period to stabilise their dosage regimen to Tegretol tablets and blinded capsules containing Tegretol tablets. They then entered an 8-week baseline period during which variation of plasma CBZ concentration was used to derive an individual Shewart Control Chart for each patient. These charts were used to define the threshold for CBZ dose reduction after the addition of trial drug. Where necessary the unblinded observer adjusted that portion of the daily dose of CBZ concealed in the opaque capsules, thereby maintaining the blind for the investigator and the patient. RESULTS: CBZ dosage reductions ranging from 14 to 50% were required by 63% of patients who received REM. Substantial increases in plasma CBZ concentration, which would have confounded the results of the trial, were thus avoided. The small increases in CBZ concentration that occurred in spite of this procedure were of similar magnitude in responders (patients who experienced > or =50% reduction in seizure frequency during treatment) and nonresponders, and in both groups the mean increase was <1 mg/L. CONCLUSIONS: The method is offered as a model solution for problems caused by pharmacokinetic interactions in add-on trials.

Acetamides↗
PubMed1997

Mutual interaction between remacemide hydrochloride and phenytoin.

A randomised, double-blind, placebo-controlled crossover study of add-on remacemide hydrochloride was carried out in epilepsy patients being treated with phenytoin (PHT) monotherapy. Eleven patients were recruited, ten of whom completed the study. Plasma concentration profiles of PHT, remacemide, and its active desglycinyl metabolite (ARL12495XX) were determined following single and multiple dosing with remacemide hydrochloride. Following 14 days' treatment with remacemide hydrochloride 300 mg twice daily, the mean AUC of PHT was increased by 11.5% (P = 0.33), Cmax by 13.7% (P = 0.32) and Cmin by 22.2% (P = 0.12) over placebo. There was an increase in trough concentrations of PHT averaging 20% during active treatment compared with placebo (P = 0.01). No symptoms of PHT toxicity were reported by any patient. There was no evidence of autoinduction of remacemide metabolism. However, average concentrations of remacemide and its active metabolite in PHT-treated patients were around 40 and 30% lower, respectively than in healthy volunteers previously receiving the same dose of remacemide hydrochloride. Thus, remacemide hydrochloride has a small inhibitory effect on PHT metabolism, which itself induces that of remacemide and its active metabolite. This mutual interaction is predictable and modest and should not present a barrier to their clinical use in combination.

Acetamides↗
PubMed1997

Lack of pharmacokinetic interaction between remacemide hydrochloride and sodium valproate in epileptic patients.

A randomized, double-blind, placebo-controlled cross-over study of adjuvant treatment with remacemide hydrochloride was carried out in 17 patients taking sodium valproate (VPA) as monotherapy. Plasma concentration profiles of VPA, remacemide, and its active desglycinyl metabolite (ARL12495XX) were determined following single (300 mg) and multiple dosing (150 or 300 mg twice daily) of remacemide hydrochloride for 14 days with a 300-mg final dose. Central nervous system side-effects were more common at the higher dose, which prompted dosage reduction to 150 mg twice daily for subsequent patients partway through the study. The mean area under the concentration-time curve, peak concentration and pre-dose concentration of VPA were unchanged by remacemide hydrochloride in three patients on the higher and in 10 patients on the lower dose of remacemide. The pharmacokinetic parameters of remacemide and its active metabolite in the VPA-treated patients were similar to those described previously in healthy volunteers. Thus, remacemide hydrochloride does not interfere with the pharmacokinetics of VPA and vice versa.

Acetamides↗
PubMed1996

Mutual interaction between remacemide hydrochloride and carbamazepine: two drugs with active metabolites.

PURPOSE: We wished to determine mutual interaction of two drugs with active metabolism: remacemide, hydrochloride and carbamazepine (CBZ). METHODS: A randomized, double-blind, placebo-controlled cross-over study of add-on remacemide hydrochloride was performed in 10 of 14 recruited patients being treated with CBZ monotherapy. Forty-eight-hour concentration profiles of CBZ, its active epoxide metabolite (CBZ-E), remacemide, and its desglycinyl metabolite (ARL12495XX) were assayed after single and multiple dosing. RESULTS: After patients were treated with 300 mg remacemide hydrochloride twice daily for 14 days, the mean area under the concentration-time curve (AUC) of CBZ was increased by 22% (p = 0.12), Cmax was increased by 27% (p = 0.07), and Cmin was increased by 22% (p = 0.29). Trough concentrations of CBZ were higher (p = 0.0037) during active treatment as compared with placebo treatment. CBZ-E levels were unaffected. No symptoms of CBZ toxicity were reported. There was no evidence of autoinduction of remacemide metabolism. However, in CBZ-treated patients, the AUC of remacemide and its active metabolite was 60 and 30%, respectively, of values observed in healthy volunteers treated previously with the same dose. CONCLUSIONS: Remacemide hydrochloride inhibits CBZ metabolism, which itself induces that of remacemide hydrochloride and its active metabolite. This mutual interaction between remacemide hydrochloride and CBZ is predictable and modest and should not present a barrier to their clinical use in combination.

Acetamides↗
PubMed1990

Treatment of glaucoma by use of transscleral neodymium:yttrium aluminum garnet laser cyclocoagulation in dogs.

Neodymium:yttrium aluminum garnet (Nd:YAG) laser energy was transsclerally applied to the ciliary body of 56 eyes of 37 dogs for treatment of glaucoma. Forty-four eyes were glucomatous at the time of treatment, and 12 normotensive eyes with ciliary cleft closure were treated prophylactically. Glaucoma was primary in 35 dogs and secondary in 2 dogs (1 eye in each dog). Energy was delivered by a general surgical Nd:YAG laser via a hand-held, 600-muc-diameter flexible quartz fiber. The mean (+/- SD) number of spots treated per eye was 35 (+/- 9.7), with mean energy per burst of 7.1 (+/- 2.6) J; mean total energy delivered to the eyes was 228 (+/- 81) J. Follow-up evaluation was available for 42 eyes from 2 to 4 weeks after treatment, and for 32 eyes from 12 to 24 weeks after treatment. Treatment success, defined as maintenance of intraocular pressure less than 25 mm of Hg, was achieved in 83% (20/24) of glaucomatous eyes evaluated between 12 and 24 weeks of treatment. Of 4 treatment failures, 3 were eyes devoid of uveal pigment. The consistent acute effects of treatment were conjunctival vascular congestion and blood-aqueous barrier disruption, recognized clinically by the presence of aqueous flare. Hyphema developed in 16% (9/56) of eyes; hyphema resolved without complication in all but 2 eyes. A common long-term complication of treatment was cataract formation, recognized in 37% (12/32) of eyes evaluated at 12 to 24 weeks. Cataracts were sufficiently dense to obstruct vision in 4 eyes. Phthisis bulbi was observed in 1 eye.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

A large multicentre, parallel group, double-blind study comparing tenoxicam and piroxicam in the treatment of osteoarthritis and rheumatoid arthritis.

A total of 1,328 patients with osteoarthritis or rheumatoid arthritis were entered into this double-blind, parallel group study of tenoxicam and piroxicam. The patient populations were well matched. An improvement was seen in pain on moving and at night in both groups and in both indications. Stiffness was also improved by both drugs, being most marked in the rheumatoid arthritis group. The primary efficacy variable was global assessment, and this showed tenoxicam to have slightly greater effect in osteoarthritis and the reverse in rheumatoid arthritis. There were no statistically significant differences in any of these findings. There were no significant differences in tolerance ratings, although the more serious gastrointestinal events occurred in the piroxicam group.

Adult↗
PubMed1981

Spinal analgesia using bupivacaine 0.5% plain. Variation in the extent of the block with patient age.

Bupivacaine 0.5% plain solution was used to produce spinal analgesia on 63 occasions. In 33 patients a fixed dose of 4 ml injected at the L2/3 interspace at 0.5 ml/second produced an extent of analgesia which was directly related to patient age (p les than 0.005). The latency was 17.3 minutes (SD 8 . 4) and duration of action was 286 minutes (SD 62). A second group receiving only 1 ml of solution had a much shorter duration of action (mean 154 minutes, SD 30). In 90% of patients the analgesia obtained was fully sufficient for surgery to be performed and no form of analgesic supplementation was given. On two occasions no analgesia occurred at all. Bupivacaine 0.5% plain proved to be an effective agent for subarachnoid block. The extent of analgesia was, however, poorly predictable, and even with low doses unacceptably high level of block were sometimes achieved.

Adult↗
PubMedDate not supplied

A multicentre study of tenoxicam for the treatment of osteo-arthritis and rheumatoid arthritis in general practice.

A study was undertaken to investigate the efficacy and tolerability of 20 mg/day tenoxicam given orally for 12 weeks in a general practice setting in a broad range of patients suffering from osteo-arthritis or rheumatoid arthritis. The group of 2963 patients was recruited from 252 general practices. Some patients (60%) continued treatment into the long-term phase of the trial, beyond 12 weeks, whereas other patients (31%) elected to continue treatment beyond 52 weeks. There was a reduction in the number of patients recording pain and stiffness over the course of the study. Adverse events were typical of a nonsteroidal anti-inflammatory drug with no unexpected or unusual side-effects. It is concluded that tenoxicam can be recommended for use in osteo-arthritis and rheumatoid arthritis.

Administration, Oral↗