Fenoterol hydrobromide (hydroxyphenylorci-prenaline; Th 1165a), which has been introduced into clinical use in Europe under a trademark (Berotec), is a sympathomimetic bronchodilator drug. The drug is chemically related to metapro-terenol (orciprenaline), but it differs because of the presence of a 4-hydroxy-phenyl radical in the isopropyl group (Fig 1). This compound may be described as a double molecule of two phenethyl radicals on a common amino group. A prior study has indicated that fenoterol is a relatively selective stimulator of /fe-adrenergic receptors, with a prolonged action; it is suitable for both oral and aerosol administration.
The object of our investigation was to establish an optimal oral dosage of fenoterol in adult patients with chronic bronchospastic disease. The drug was compared with ephedrine, administered in the accepted oral dosage, and with a placebo.
Materials and Methods
Twenty subjects with a diagnosis of reversible obstruction of the airways (Table 1) volunteered to participate in this clinical study; all signed forms indicating informed consent following approval of the study by the institutional committee on human research. The ages of the patients ranged from 30 to 74 years; 14 of the 20 patients were women. Participants were evaluated by history, clinical examination, electrocardiogram, chest x-ray film, and tests of pulmonary function. Volunteers were excluded if they had a history or evidence of significant hematologic, renal, hepatic, cardiac, or cerebral disease or if they were potentially fertile women. For inclusion in the study, each patient had to demonstrate an increase of 20 percent or more in the forced expiratory volume in one second (FEVi) following two metered inhalations (0.075 mg of isoproterenol sulfate each).
The study was conducted in double-blind fashion, with each patient receiving, in a crossover design, ephedrine (24 mg), placebo, and fenoterol hydrobromide (5 mg, 7.5 mg, and 10 mg). The sequence of treatments was randomized, except that the various doses of fenoterol were in the order of increasing strength. Each of the five testing agents was administered at the same hour of the morning, at intervals of at least 24 hours. No short-acting bronchodilator or other sympathomimetic drugs were permitted for eight hours and no long-acting bronchodilator drugs for 12 hours prior to the administration of each testing agent.
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Variables of pulmonary function were measured on each day of testing before administration of any testing agent (baseline), and at one, two, three, four, five, six and eight hours after the testing doses. The FEVi, the forced vital capacity (FVC), the mean forced expiratory flow during the middle half of the FVC (FEF25-75%), and the peak expiratory flow (PEF) were measured using a spirometer (model 220), a Pulmo-Norm Digitizer (model 560), a digital printer (model 790), and an X-Y recorder (model 750) (all from (Cardio Pulmonary Instruments Corp.). Thoracic gas volume (VtK) and airway resistance (Raw) were determined by using a whole-body plethysmograph (Warren E. Collins, Inc.), and specific airway conductance (Gaw/Vb) was calculated. Respiratory loops were displayed on a storage oscilloscope (Tektronix, Inc.) and were recorded for later analysis using video-tape equipment (Sony Videocamera AVC 3210 and* Sanyo portable video cassette recorder-player VTC 7100) and a specially modified monitor. The values used were the average of duplicate determinations.
Pulse rate and blood pressure were recorded at the times that the variables of pulmonary function were measured. Routine clinical laboratory tests were performed at the beginning and at the conclusion of the study; these included a complete blood cell count, urinalysis, and standard renal and hepatic tests.
Figure 1. Structural formulae of fenoterol and related compounds.
Table 1 — Characteristics of Patients
| Patient, Age (yr), Sex | Weight, kg (lb) | Diagnosis-A.> | Duration,yr | |
| Primary | Secondary | |||
| 201, 54, M | 59 (130) | Bronchitis | Asthma | 5 |
| 202, 51, F | 59 (130) | Bronchitis | Emphysema | 25 |
| 203, 67, M | 102 (225) | Asthma | Bronchitis | 30 |
| 204, 48, F | 73 (162) | Asthma | 10 | |
| 205, 65, M | 81 (179) | Asthma | 10 | |
| 206, 61, M | 66 (145) | Bronchitis | Asthma | 8 |
| 207, 56, M | 78 (172) | Asthma | Bronchitis | 6 |
| 208, 53, F | 59 (130) | Asthma | Bronchitis | 5 |
| 209, 63, F | 65 (244) | Asthma | Bronchitis | 6 |
| 210, 42, F | 73 (162) | Asthma | Bronchitis | 10 |
| 211, 74, F | 54 (120) | Bronchitis | 5 | |
| 212, 47, M | 48 (106) | Asthma | Emphysema | 47 |
| 213, 60, F | 95 (210) | Asthma | Emphysema | 25 |
| 214, 38, F | 59 (130) | Asthma | 5 | |
| 215, 30, F | 90 (198) | Asthma | … | 6 |
| 216, 66, F | 76 (168) | Asthma | 15 | |
| 217, 50, F | 73 (160) | Asthma | Bronchitis | 24 |
| 218, 62, F | 68 (150) | Asthma | Bronchitis | 5 |
| 219, 51, F | 79 (175) | Emphysema Bronchitis | 8 | |
| 220, 60, F | 43 (94) | Emphysema Asthma | 3 | |