Gossypol and Furosemide Injection: Interaction Details

a) Gossypol reduced serum potassium levels in a double-blind, randomized, controlled study of 152 male volunteers to evaluate the efficacy of gossypol as a male contraceptive. Gossypol 20 milligrams (mg) was taken by 75 subjects per day initially, followed by a maintenance phase of 50 mg/week, and continued treatment for at least 14.5 months. One patient experienced a decrease in serum potassium level from 4.8 milliequivalents per liter (mEq/L) on admission to 3.7 mEq/L at the end of the loading phase (2.5 months), which then declined further to 2.6 mEq/L, after which treatment was stopped. An additional patient whose potassium was 3.5 mEq/L at admission declined to 2.4 mEq/L at 9 months, after which treatment was stopped. In the entire treatment group, potassium levels were 4.3 +/- 0.03 mEq/L at admission and 3.8 +/- 0.04 mEq/L after 14.5 months of gossypol use (p less than 0.05) ¹.

b) Potassium loss was not deterred by coadministration of triamterene or supplementation with potassium in a randomized trial with 120 male volunteers. Volunteers received gossypol alone, gossypol plus potassium salt 1.5 grams daily, gossypol plus triamterene 50 mg daily, or no treatment. Gossypol treatment began with a 60 day loading phase of gossypol 20 mg daily, followed by gossypol 50 mg weekly for 10 months. At the end of the 60 day loading phase, potassium levels declined in gossypol treated groups, but not the control group (p less than 0.05). At the end of the maintenance phase, average serum potassium was 3.98 mEq/L in the gossypol group, 4.11 mEq/L in the gossypol/potassium supplementation group, 3.77 mEq/L in the gossypol/triamterene treated group, and 3.92 mEq/L in the control group. All gossypol treatment groups had potassium levels significantly lower at the end of the maintenance phase versus admission (p less than 0.05). One case of hypokalemic paralysis (serum potassium 2.0 mEq/L) occurred one month after the end of treatment with gossypol and triamterene. It was hypothesized that gossypol may cause renal impairment, such that potassium supplementation or blocking agent such as triamterene may not affect return of potassium levels to normal even after gossypol treatment is stopped ².

c) Two patients taking gossypol for metastatic adrenal cancer developed hypokalemia two to three weeks after gossypol discontinuation. Serum potassium levels were 2.3 millimoles/liter (mmol/L) and 2.6 mmol/L (normal range 3.5 to 4.0 mmol/L) ³.

d) Over a 5-year period, 148 men took gossypol as a contraceptive. Seven men (5%) developed hypokalemic paralysis with associated serum potassium levels of 2 mEq/L to 2.73 mEq/L. It was noted that dietary potassium intake was low in these men and may have increased their risk of this adverse effect. Renal potassium excretion studies led to the conclusion that the majority of gossypol-related cases of hypokalemia involved renal potassium loss ⁴.