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Crit Care Med. 2002 Apr;30(4):820-6.

Intravenous colforsin daropate, a water-soluble forskolin derivative, prevents thiamylal-fentanyl-induced bronchoconstriction in humans.

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  • 1Department of Anesthesia, Chiba Hokusoh Hospital, Chiba, Japan. HFB01245@nifty.com

Abstract

OBJECTIVE:

Forskolin, a direct activator of adenylate cyclase, can relax airway smooth muscle, similar to other agents that increase intracellular cyclic adenine monophosphate. However, the potential usefulness of forskolin in treating bronchospasm is limited by its poor water solubility. Colforsin daropate is a novel and potent water-soluble forskolin derivative. No clinical data have been published on the bronchorelaxant effects of this drug. The aim of this study was to investigate whether intravenous colforsin daropate prevents thiamylal-fentanyl-induced bronchoconstriction.

DESIGN:

Double-blind, prospective, placebo-controlled randomized study.

SETTING:

University teaching hospital.

PATIENTS:

Thirty-six patients were allocated randomly to two groups: the control group (n = 18) and colforsin daropate group (n = 18).

INTERVENTIONS:

Intravenous administration of colforsin daropate or placebo (normal saline).

MEASUREMENTS AND MAIN RESULTS:

Anesthesia was induced with thiamylal 5 mg/kg and vecuronium 0.3 mg/kg. A 15 mg x kg(-1) x hr(-1) continuous infusion of thiamylal followed anesthetic induction. Controlled ventilation was maintained, delivering 50% nitrous oxide in oxygen. Twenty minutes after the induction of anesthesia, the control group patients started to receive 7.5 mL/hr continuous infusion of normal saline, and the colforsin daropate group patients started to receive 0.75 microg x kg(-1) x min(-1) (7.5 mL/hr) continuous infusion of colforsin daropate for 60 min. After that, both groups received fentanyl 5 microg/kg. Systolic and diastolic arterial pressure, heart rate, mean airway resistance (Rawm), expiratory airway resistance (Rawe), and dynamic lung compliance (Cdyn) were measured at the baseline, just before the administration of fentanyl (T30), at three consecutive 6-min intervals after fentanyl injection (T36, T42, and T48) and 30 min after fentanyl injection (T60). At baseline, both groups had comparable Rawm, Rawe, and Cdyn values. In the control group, Rawm increased significantly at T36-60 compared with the baseline, Rawe increased significantly at T36-48 compared with the baseline, and Cdyn decreased significantly at T36-60 compared with the baseline. In the colforsin daropate group, there were no changes in Rawm, Rawe or Cdyn at T36-60.

CONCLUSIONS:

These observations suggest that intravenous colforsin daropate has a bronchodilator effect in humans.

PMID:
11940752
[PubMed - indexed for MEDLINE]
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