Sublingual administration of furosemide: new application of an old drug

Abstract

Background: In patients with decompensated heart failure, absorption of orally administered furosemide may be delayed, possibly leading to impaired pharmacodynamic effects. Sublingual administration may represent an alternative in such situations.

Methods: In a crossover study including 11 healthy men, 20 mg furosemide was administered intravenously, orally and sublingually on three different days. Pharmacokinetics and pharmacodynamics were assessed from repeated blood and urine samples.

Results: Compared with oral administration, sublingual administration was associated with 43% higher C(max)[difference 215 ng ml(-1), 95% confidence interval (CI) 37, 392], a higher urinary recovery (8.9 vs. 7.3 mg, difference 1.6 mg, 95% CI 0.3, 2.9), an 28% higher AUC (difference 328 ng h(-1) ml(-1), 95% CI 24, 632) and a higher bioavailability of furosemide (59 vs. 47%, difference 12.0%, 95% CI -1.2, 25.2). Sodium excretion was higher after sublingual compared with oral administration (peak excretion rate 1.8 vs. 1.4 mmol min(-1), P < 0.05), whereas urine volume did not differ significantly between the two application modes. In comparison, intravenous administration showed the expected more rapid and intense response.

Conclusion: Sublingually administered furosemide tablets differ in certain kinetic and dynamic properties from identical tablets given orally. Sublingual administration of furosemide may offer therapeutic advantages in certain groups of patients.

Figure 1

Plasma concentration time-curve (A) and cumulative urinary excretion (B) of 20 mg furosemide, administered intravenously (IV), sublingually (SL), or orally (PO) (mean ± SEM). See Table 1 for pharmacokinetic constants. Intravenous, (○); oral, (); sublingual, ()

Figure 2

Renal excretion rate (A) and cumulative excretion (B) of sodium after 20 mg of furosemide intravenously, sublingually or orally (mean ± SEM). Oral, (); sublingual, (); intravenous, (○)

Figure 3

Relation between urinary excretion rates of furosemide and sodium after treatment with 20 mg furosemide intravenously, sublingually or orally. Intravenous, (○); oral, (); sublingual, ()

Figure 4

Urine excretion rate (A) and cumulative urine excretion (B) after 20 mg of furosemide intravenously, sublingually or orally (mean ± SEM). Oral, (); sublingual, (); intravenous, (○)