application of mind objective: Assessment of acute and chronic issues of low-dose almitrine bismesylate (AB) in stable chronic obstructive pulmonary disease (COPD) thought design: Oral administration of AB.

application of mind objective: Assessment of acute and chronic issues of low-dose almitrine bismesylate (AB) in stable chronic obstructive pulmonary disease (COPD)

thought design: Oral administration of AB, 25 mg three times a day, for 6 month in all patients. Pulmonary function, vital current gases, and peripheral nerve conduction velocity were measured at baseline and after long-term administration of AB. In addition, oral pharmacokinetics and general intents on pulmonary circulation at stillness were studied in half of the patients. Intravenous pharmacokinetics were measured after a single intravenous dose of 60 mg of AB 3 month before the start of oral AB treatment in the other seven patients.

Setting: Outpatient clinic of a community hospital in a coal mining district in southwest Germany.

Patients: Fourteen patients with clinically stable COPD and hypoxemia.

Results: Acute purports of AB were as follows: a significant increase in arterial oxygen tension ([PaO.sub.2]) from 61 [+ or -] 7 mm Hg to 74 [+ or -] 8 mm Hg (p [les than] 0001) a decrease in arterial carbon dioxide tension ([PaCO.sub.2]) from 41 [+ or -] 8 mm Hg to 38 [+ or -] 7 mm Hg (p [les than] 001) a rise of pH from 745 [+ or -] 004 to 748 [+ or -] 004 (p [les than] 001) and a transient increase in mean pulmonary artery squeezing from 26 [+ or -] 7 to 29 [+ or -] 6 mm Hg (not significant). After long-term treatment, formerly tissues were saturated with almitrine, improvement in gas exchange persisted with a [PaO.sub.2] of 70 [+ or -] 10 mm Hg (p [les than] 0001) and a [PaCO.sub.2] of 39 [+ or -] 6 mm Hg (not significant) without elevation of pH (745 [+ or -] 004) or of pulmonary artery hurry (26 [+ or -] 8 mm Hg) The terminal half-life of AB was 56 [+ or -] 45 days after a single intravenous administration, and 55 [+ or -] 16 days after long-term oral dosing. None of the patients exhibited clinically manifest peripheral neuropathy. Impaired asymptomatic peripheral motor brace function was prevalent in 4 (29 percent) of the patients and remained unchanged during long-term AB administration. However, asymptomatic impairment of motor strengthen conduction velocity developed in brace patients with inadequate high AB plasma on a levels despite low-dose therapy. the couple patients were known to have additional conditions predisposing for neuropathy.

Conclusions: Low-dose AB therapy, 75 mg daily, terminateed in sustained elevation of arterial oxygen tension in hypoxemic patients with COPD Although pulmonary artery press increased transiently after the first dose, it remained unchanged with long-term treatment despite persistent improvement of pulmonary gas exchange. Monitoring of AB plasma horizontals is advisable in select patients during long-term administration to avoid neuropathy, on a level with such a low daily dose.

Patients with chronic obstructive pulmonary disease (COPD) characteristically have a reduc arterial oxygen tension ([PaO.sub.2]), repeatedly accompanied by an increase in arterial carbon dioxide tension ([PaCO.sub.2]). The long-term prognosis of patients with COPD is poor, especially after the charge of severe hypoxemia.[1] Long-term domiciliary oxygen therapy is the single treatment that has been shown to improve survival.[2] Almitrine bismesylate (AB) is a recent drug that has been classified as a peripheral chemoreceptor agonist of the carotid and aortic bodies.[3] The compose induces a significant and persistent increase in arterial oxygen tension of 5 to 10 mm Hg in mostly hypoxemic patients with COPD at a daily dose of 100 mg[4] In contrast to oxygen therapy, the physic also reduces hypercapnia.[5-8] However, at doses of 100 to 200 mg/d for 6 to 12 month side forces such as increased dyspnea and peripheral paresthesia are often met with almost certain due to an accumulation of the drug

Therefore, the view of this study was to evaluate whether low-dose AB, 25 mg three times a day, was tolerated better and whether the agent was still effective in the treatment of hypoxemia.

METHODS

Subjects

Fourteen patients with hypoxemia becoming to chronic obstructive lung disease were registered in the study after having given written informed co-operation The selection criteria for entrance into the study were the same as in the VIMS study[5] and included the following: (1) no previous oxygen treatment; (2) [PaO.sub.2] [les than or equal to] 65 mm Hg with a variation [les than or equal to] 6 mm Hg in three measurements during the previous 3 weeks; (3) [PaCO.sub.2] [greater than] 35 mm Hg; (4) age between 35 and 75 years; (5) [FEVsub1]/FVC ratio between 25 and 65 percent and [FEVsub1] [les than or equal to] 70 percent of the predicted value; and (6) les than 2 kg variation in weight within the previous 3 weeks.

Exclusion criteria were as follows: (1) clinically unstable chronic bronchitis and emphysema (CBE), eg adventure of three exacerbations of the disease within the past year or single in kind exacerbation within the previous 6 weeks; (2) clinically unstable right or left heart failure; (3) a history of pulmonary embolism; (4) unstable angina or myocardial infarction within the previous 3 months; (5) renal failure (creatinine [greater than] 180 [mu]mol/L); and (6) abnormal ends of liver function tests. Almitrine bismesylate was administered in addition to the usual long-term medication. The concomitant medicine regimen was kept constant, as frequently as possible, throughout the subject of attention The study was performed in the outpatient clinic of the Department of Medicine, St Elisabeth Clinic, Saarlouis (former affiliation of first author). The 500-bed clinic besufficient fors as a community hospital for the region, which has been dominated, until now, through the steel and coal mining industry. Thus, six of the patients were coal miners with more than 30 years of active duty; the occupation of the remaining patients was hairdresser (two) locksmith (two) floor tiler (one) white collar worker (two) and housewife (one)

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