Terfenadine treatment of fall hay fever.

A double-blind, parallel, multicenter study was undertaken in 215 ragweed skin test positive-patients with fall hay fever. The patients were randomized and treated for seven days with either 60 mg terfenadine twice daily, morning and evening, and a placebo at noon, or with 4 mg chlorpheniramine or placebo three times daily. The severity of nasopharyngeal itching, sneezing, rhinorrhea, nasal congestion, and itchy, watery, red eyes was ranked daily by patients and evaluated before and after treatment by the physician investigators. The patients reported a significant reduction in symptoms within one day. The physician investigators detected moderate to complete relief of symptoms in a greater proportion of the patients treated with terfenadine (70%) and chlorpheniramine (73%) than in the placebo-treated patients (48%). The incidence of sedation with terfenadine treatment (2.5%) was not different from that with placebo (2.4%) and both were lower than with chlorpheniramine (7.6%). We conclude that terfenadine is as effective as chlorpheniramine for the treatment of fall hay fever and that, unlike chlorpheniramine, the incidence of sedation with terfenadine was not different from placebo.

Multicenter, double-blind, placebo-controlled trial of terfenadine suspension in the treatment of fall-allergic rhinitis in children.

Children, aged 6 to 12 years, with fall-pollenosis symptoms, were evaluated for their response to a new antihistamine, terfenadine, in a multicenter (six centers) 1-week, double-blind, placebo-controlled trial. All had positive skin tests to grass/weed pollens and/or mold spores prevalent in the fall at each center. Patients were administered placebo or terfenadine as suspension on a randomized basis, with children weighing less than 30 kg receiving terfenadine suspension, 30 mg twice daily, and those weighing greater than 30 kg receiving 60 mg, twice daily. Of the 119 children enrolled, 79 received terfenadine and 40 received placebo. All but two (lost to follow-up) were included for the evaluation of drug safety, whereas 16 were excluded from the efficacy evaluation (11 receiving terfenadine and five receiving placebo) because of protocol noncompliance. Overall, varying degrees of control of symptoms were observed in 85% of the patients in the group taking terfenadine as compared to 60% in the group taking placebo. The symptoms of rhinorrhea, nasal congestion, and sneezing demonstrated the best response. There was no difference between the two groups in adverse events or side effects. Before and after treatment complete blood count, biochemical profile, and urinalysis revealed that there was no change from beginning to end and no difference between the groups. We conclude that terfenadine suspension is a safe, nonsedating antihistamine with an incidence of side effects no different from that of placebo. It is more effective than placebo in controlling symptoms of fall pollenosis in children.

Studies on the mechanism of the cardiotonic activity of MDL 19205: effects on several biochemical systems.

MDL 19205, 4-ethyl-1,3-dihydro-5-(4-pyridinyl-carbonyl)-2H-imidazol-2-one, is a new drug with cardiotonic properties. Its effects on several biochemical systems considered to be important in myocardial contraction were investigated. Cyclic nucleotide phosphodiesterases (PDEs) from dog hearts were separated into three isoenzymes, F I, F II, and F III, and effect of the drug on these enzymes was tested. MDL 19205 inhibited F III PDE specifically and produced little or no inhibition of F I and F II PDEs. The IC50 for inhibition of F III PDE was 8.6 microM when 0.5 microM cyclic AMP (cAMP) was used, whereas no more than 10% inhibition of F I and 18% of F II PDEs occurred at drug concentrations up to 200 microM when 1 microM cAMP was used. Concentrations of MDL 19205 up to 100 microM had no effect on Ca2+-adenosine triphosphatase (ATPase) or Ca2+ uptake by dog cardiac sarcoplasmic reticulum. At 100 microM, the drug produced a weak (18%) inhibition of Na+,K+-ATPase. It is suggested that inhibition of F III PDE may be the primary mechanism by which MDL 19205 produces its cardiotonic effect. Inhibition of Na+,K+-ATPase may also be involved at very high concentrations of this drug.

Biochemical studies on the mechanism of cardiotonic activity of MDL 17,043.

MDL 17,043 (1,3-dihydro-4-methyl-5-[4-(methylthio)-benzoyl]-2H-imidazol-2-one) is a new drug with cardiotonic properties. Its effects on several biochemical systems considered to be important in myocardial contraction were investigated and compared with those produced by amrinone and theophylline. Dog cardiac phosphodiesterases (PDEs) were separated into three major forms and labeled PDE I, II, and III according to the order of elution during isolation by column chromatography. PDE I and II, considered to be "high-Km" enzymes for cyclic AMP, were not inhibited by MDL 17,043, amrinone, or theophylline in concentrations of 50 microM. PDE III, a "low-Km" enzyme, was strongly inhibited by MDL 17,043. Kinetic studies showed the inhibition to be characteristic of partial competitive inhibition. At 0.25 microM cyclic AMP, 1.3 microM MDL 17,043 caused 50% inhibition of PDE III (I50), while the I50 for amrinone and theophylline were estimated to be 19.5 microM and 119 microM, respectively. Dog kidney Na+, K+-ATPase was inhibited 54% by 100 microM MDL 17,043 while amrinone caused an 18% inhibition at the same concentration. Ca2+-ATPase and Ca2+ uptake by dog sarcoplasmic reticulum vesicles were unchanged by MDL 17,043 concentrations up to 300 microM and 100 microM, respectively. It is suggested that the inhibition of PDE III is related to the cardiotonic effects produced by MDL 17,043 and amrinone, although inhibition of Na+, K+-ATPase may also play a role at high concentrations of these drugs.