Adjuvant laser acupuncture in the treatment of whiplash injuries: a prospective, randomized placebo-controlled trial.

UNLABELLED: Following introduction of the compulsory use of seat belts in cars, whiplash injuries of the cervical spine have become common in everyday practice. Current treatment approaches lead to resolution of the symptoms within a short time in most cases but cannot prevent a small proportion of patients developing persistent health problems. The effects of adjuvant treatment with laser acupuncture on the acute symptoms and the results one year after the injury were studied in this prospective, randomized, placebo-controlled single-blind study. One group of patients (n = 23) were treated with laser acupuncture (5 mW HeNe laser on 22 acupuncture points for 15 s each) plus cervical collar and a combination of paracetamol and chlormezanone; a second group (n = 22) received the same treatments but with the use of a placebo laser. The treatment was given three times per week until the patient was asymptomatic. No statistically significant advantage of the laser acupuncture treatment was found in the acute phase (mobility in all three planes, duration of pain and duration of use of a cervical collar) or the chronic phase (drug use and the incidences of chronic recurrent problems such as myofascial pain, headaches, vertigo and tinnitus). CONCLUSION: Adjuvant laser acupuncture with a 5 mW HeNe laser and an irradiation time of 15 s appears to be ineffective in the management of whiplash injuries.

Relative bioavailability of 3 different chlormezanone 200 mg preparations after single dose oral administration.

Eighteen male volunteers have been treated with 3 different oral formulations of chlormezanone according to a randomized 3-way change-over design. The test preparation was a tablet (Krewel), reference preparation 1 was a suspension (Krewel), and reference preparation 2 was a tablet (Muskel Trancopal, Sanofi Winthrop GmbH). All preparations contained 200 mg of chlormezanone. Divided in 3 periods the volunteers received single doses of the test and the 2 reference formulations, respectively. Blood samples have been drawn immediately prior to each administration and at 21 sampling points within 144 h after dosing. A wash-out period of 2 weeks was maintained between successive drug doses. Plasma concentrations of chlormezanone were determined by a validated reversed-phase HPLC method with UV detection, with a lower limit of quantification of 0.1 microgram/ml. The following mean values have been obtained for the test preparation: AUC0-infinity 121 micrograms x h/ml, Cmax of 2.9 micrograms/ml at 1.5 h, t1/2 38 h, after administration of the suspension: AUC0-infinity 111 micrograms x h/ml, Cmax 2.6 micrograms/ml, tmax 1.5 h, t1/2 40 h, and after administration of the reference tablet: AUC0-infinity 121 micrograms x h/ml, Cmax 3.0 micrograms/ml, tmax 1.6 h, t1/2 38 h. The test preparation shows a relative bioavailability of 109% compared to the suspension and has been proven to be bioequivalent to the reference tablet with regard to extent and rate of absorption.

[Flupirtine in comparison with chlormezanone in chronic musculoskeletal back pain. Results of a multicenter randomized double-blind study]. / Flupirtin im Vergleich zu Chlormezanon und Plazebo bei chronischen muskuloskelettalen Rückenschmerzen. Ergebnisse einer multizentrischen randomisierten Doppelblindstudie.

METHOD: The analgesic and muscle-relaxing properties of flupirtine maleate, chlormezanone and placebo were compared in a total of 184 patients. Of these patients, 164 met the criteria of the treatment plan (intention to treat), and the data of 140 patients were finally evaluated in accordance with the test protocol. A positive response was defined as a reduction in pain intensity and muscle tension by 2 categories on the 5-category verbal scale "very severe/severe/moderate/mild/ none" on the seventh day of treatment. RESULTS: In the per-protocol-analysis the responder rate was 60.9% for flupirtine, 47.8% for chlormezanone, and 43.8% for placebo, the difference between drugs and placebo not being significant. The overall assessment of the physicians involved was very good/ good in 47.8% and satisfactory in 37.0% of the flupirtine group, very good/good in 45.6% and satisfactory in 17.4% of the chlormezanone group, the corresponding figures for the placebo group being 33.4% and 20.6%, respectively. Flupirtine was thus superior to placebo (p = 0.007). The incidence of adverse drug reactions was 14.8% (8/54) for flupirtine, 19.3% (11/57) for chlormezanone, and 7.3% (4/55) for placebo.

Chlormezanone plasma and blood levels in patients after single and repeated oral doses and after suicidal drug overdose.

Chlormezanone plasma concentrations were determined in 5 volunteers (group 1) after a single oral dose of 200 mg of chlormezanone with high performance liquid chromatography. A plasma elimination half-life of 23 +/- 2.3 h was calculated. The mean peak chlormezanone plasma level was 1.86 +/- 0.2 micrograms/ml, 1 h after ingestion. Additionally, chlormezanone plasma levels were determined after repeated oral doses of chlormezanone recommended for treatment of muscular spasms due to degenerative skeletal disease. After 5 days of repeated daily doses of 3 x 200 mg (group 2; 12 patients) or 3 x 400 mg (group 3; 10 patients) of chlormezanone, mean predose chlormezanone plasma levels were 12.0 +/- 2.0 micrograms/ml (group 2) and 22.7 +/- 4.0 micrograms/ml (group 3), respectively. Comparable plasma concentrations were determined after 10 days of repeated doses of 3 x 200 mg or 3 x 400 mg of chlormezanone in 3 patients from each of these 2 groups. In 7 patients of group 3, chlormezanone had to be discontinued on the 5th day due to increasing muscular weakness, ataxia and exercise-inducible tachycardia. After a loading dose of 800 mg and repeated doses of 3 x 200 mg chlormezanone to 5 patients (group 4), plasma levels of 6.5 +/- 2.1 micrograms/ml, 8.9 +/- 2.2 micrograms/ml, 12.7 +/- 2.0 micrograms/ml, and 10.4 +/- 2.4 micrograms/ml were determined after 2, 8, 16, and 36 h, respectively. Trace amounts of a degradation product of the acid-labile chlormezanone could be detected in plasma besides the unchanged drug after administration of repeated oral doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of chlormezanone in elderly patients.

The pharmacokinetics of Chlormezanone (CM) has been determined after a single oral dose of 400 mg CM in 5 young volunteers (28 y) and in 8 elderly patients (79 y). In the young subjects, CM was rapidly absorbed and distributed, and was slowly eliminated with a half-life of 38 h major metabolites were not detected in plasma or urine. Only 3% of CM was excreted unchanged in urine. In elderly patients absorption was delayed but not reduced; the Cmax and AUC did not differ from those in younger subjects, the elimination rate was reduced compared to the younger subjects (mean 54 h). The increase was in part related to the reduction in renal function and metabolism observed in aging. However, the change in pharmacokinetics was moderate and no adjustment in dosage seems necessary for treatments of limited duration in elderly patients.

[Pharmacokinetics of chlormezanone in healthy volunteers]. / Pharmacocinétique de la chlormézanone chez le volontaire sain.

The kinetics of chlormezanone were determined after oral administration of single (400 mg) and multiple doses (400 mg/day during 8 days) in eight young healthy male subjects. Plasma levels determination had been carried out by HPLC. After single dose administration, Cmax concentrations 4.62 +/- 0.75 mg/l were obtained (Tmax) 2.18 +/- 1.49 h after drug intake. Area under plasma concentrations time curve was 224.93 +/- 27.79 mg.h/l and terminal half-life 40.50 +/- 4.19 h. On chronic regimen, chlormezanone accumulates in the body: trough plasma concentrations are significantly increased from Day 7 (2.97 +/- 0.45 mg/l) to Day 9 (5.41 +/- 0.90 mg/l) and reach the steady state faster than it can be expected from half-life (40 hours) and dosing interval (24 hours). Elimination is faster (T1/2 beta = 37.14 +/- 3.18 h) after chronic regimen. Area under curve during dosing interval at steady state (164.19 +/- 21.70 mg.h/l) is significantly lower than the area under curve between zero and infinity in the single dose sequence (224.93 +/- 27.79 mg.h/l). These results agree with probable induction effect of chlormezanone on its own metabolism.

Four-week tolerance study of chlormezanone for the treatment of insomnia in the elderly.

A 4-week study of chlormezanone was carried out in thirty-two patients admitted to a geriatric ward and requiring regular night sedation. Two patients required 400 mg nightly, the remainder only 200 mg nightly. The duration and quality of sleep, and frequency of awaking refreshed, all improved during chlormezanone therapy. There was no deterioration in mental agility test performance. There were no serious side-effects, no significant changes in blood urea or liver function tests, and no evidence of drug accumulation. It is concluded that chlormezanone appears to be a well tolerated drug for elderly patients with sleep disturbance meriting further controlled evaluation.

A double-blind study of benorylate and chlormezanone in musculoskeletal disease.

In a double-blind, cross-over study of 90 patients with degenerative disease of the hip, knee, cervical or lumbar spine, and capsulitis of the shoulder the analgesic drug benorylate (either alone or in combination with chlormezanone, a muscle relaxant anxiolytic drug) favourably modified pain, stiffness, quality of sleep and ability to work. Chlormezanone significantly reduced the number of breaks in sleep. There was no significant difference in the number of patients reporting side-effects on each of the four treatments, but drowsiness occurred significantly more in the chlormezanone weeks. There appeared to be no advantage in adding chlormezanone in patients suffering from osteoarthritis of the hip or knee, lumbar spondylosis or capsulitis of the shoulder, but there was significant improvement in both pain relief and quality of sleep in those patients with neck pain.

A single dose placebo-controlled study to assess the effectiveness of adding a muscle relaxant to a compound analgesic in the treatment of tension headache.

A patient-assessment of pain relief over 4 hours following a single dose of a compound analgesic has shown that 78% of patients achieve satisfactory relief of pain due to tension headache and that this response is enhanced by the addition of chlormezanone, an agent with reported anxiolytic and muscle relaxant actions. Side-effects were minor in nature.

A controlled study of Trancopal in sleep disturbances due to rheumatic disease.

A placebo controlled, double-blind study was carried out in six centres in general practice to assess the effectiveness of Trancopal in treating sleep disturbances due to rheumatic disorders. Eighty-five patients received a usual dose of two tablets of Trancopal or matching placebo at night for two weeks. Patients were assessed weekly and kept a daily record of the quality of sleep. All ratings showed that patients slept significantly better on Trancopal than on placebo. Day-time rheumatic stiffness however was not significantly reduced. Six patients receiving Trancopal reported side-effects chiefly drowsiness (five patients) which was controlled by dose reduction. It was concluded that for rheumatic patients Trancopal offers an acceptable alternative to current hypnotics over which it may prove to have some advantages, particularly for the elderly.

A controlled study of Trancopal in the treatment of sleep disturbances due to anxiety.

Sixty-eight patients presenting with sleep disturbances due to mild neurotic anxiety were treated for two weeks with a single night-time dose of 400 mg trancopal or matching placebo under double-blind conditions. Patients kept a daily record of the quality of their sleep and the observer carried out a weekly rating of anxiety using a modified Hamilton scale. By Day 7 patients receiving Trancopal had a significantly better rating for sleep and mean Hamilton scores for day-time anxiety than the placebo group. Side-effects were minimal. It was concluded that for patients with sleep disturbances due to neurotic anxiety Trancopal is a well tolerated and effective alternative to the hypnotics.

[Electroencephalographic effects of chlorphenesin carbamate, a new central muscle relaxant, in rabbits (author's transl)].

Electroencephalographic (EEG) effects of chlorphenesin carbamate were investigated in rabbits with chronic electrode implants, and compared with those of chlormezanone and methocarbamol. Chlorphenesin carbamate (50 mg/kg i.v., 100 mg/kg i.d.) induced a drowsy pattern of spontaneous EEG consisting of high voltage slow waves in the cortex and amygdala, and desynchronization of hippocampal theta waves. Chlormezanone also elicited similar EEG changes but such were much more potent than chlorphenesin carbamate. Methocarbamol showed no effect on spontaneous EEG. Chlorphenesin carbamate caused sedation in this period and muscle relaxation was more potent than that of chlormezanone. The EEG arousal response to auditory stimulation and to electric stimulation of the posterior hypothalamus, centromedian thalamus and mesencephalic reticular formation was slightly depressed by chlorphenesin carbamate. Chlorphenesin carbamate, as with chlormezanone, markedly depressed the limbic afterdischarges elicited by hippocampal stimulation. These EEG effects of chlorphenesin carbamate were qualitatively similar to but much weaker than those of chlormezanone, whereas the muscle relaxant effect of chlorphenesin carbamate was more potent than that of chlormezanone.