Pharmacokinetics of 14C-delmopinol in the healthy male volunteer.
1. The absorption and excretion of delmopinol, an inhibitor of plaque formation and gingivitis, were studied in healthy male volunteers. Each subject received a single dose of a 10-ml aqueous solution of 14C-delmopinol at 2 mg/ml as a 1-min mouth rinse (the intended route of administration; n=6) or as an oral dose (n=6). 2. After mouth rinsing, 72% of the dose was expectorated. The retained portion of the dose was rapidly absorbed and eliminated. Of the dose, 25% was recovered in the urine. Renal excretion was predominant also after oral administration with 92% of the dose excreted in the urine. The total recovery of 14C-activity after 6 days was 99% (rinsing) and 95% (oral) with the bulk, 20% (rinsing) and 80% (oral), of the dose excreted already within 8 h. 3. Peak plasma levels of 14C-labelled compounds were attained at 1.5 h after rinsing and 0.5 h after oral administration; total concentrations were approximately 200 and 3000nmol/l, respectively. For parent delmopinol, peak plasma levels of 49 nmol/l (rinsing) and 8 nmol/l (oral) occurred after 1.5 and 1.3 h, respectively. After rinsing, the concentration of delmopinol declined with a half-life of 2.4 h. The plasma level of 14C-labelled compounds declined multiphasically. In the terminal elimination phase (after 72 h) remaining radioactivity, < 2% of dose (rinse) and < 5% of dose (oral), decreased with a half-life of approximately 130 and 160 h, respectively. 4. Results indicate a very low bioavailability (1-3%) due to extensive first-pass metabolism of delmopinol after oral administration. A high plasma clearance (> 60 l/h) and a large volume of distribution (> 200 l) were also indicated. 5. The results of rapid and almost complete recovery in the urine support that delmopinol can safely be used in the treatment of patients with plaque or gingivitis.
Eriksson
B
B
Pharmacokinetics and Metabolism, Lund Research Center AB, Active Biotech, Sweden.
Ottersgård Brorsson
A K
AK
Hallström
G
G
Sjödin
T
T
Gunnarsson
P O
PO
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D002250:Carbon Radioisotopes; D005243:Feces / Q000737:chemistry; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D009067:Mouthwashes / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D014556:Urine / Q000737:chemistry
D002250:Carbon Radioisotopes; D009025:Morpholines; D009067:Mouthwashes; C073738:delmopinol