Cicletanine-induced hyponatremia and hypokalemia in kidney transplant patients

BACKGROUND: Cicletanine is an antihypertensive agent with vasorelaxant and diuretic properties. It has been widely used in European countries; however, cicletanine-associated electrolyte disturbances have yet to be defined. We investigated cicletanine-induced hyponatremia and hypokalemia in kidney transplant patients. METHODS: Data from a total of 68 kidney transplant recipients who were treated for hypertension with cicletanine were retrospectively analyzed. Cicletanine-induced hyponatremia and hypokalemia were defined as serum sodium < 135 mmol/L and potassium < 3.5 mmol/L, respectively, after the use of cicletanine. RESULTS: The average patient age was 50 (±11) years, and 44 (65%) were male. The daily dose of cicletanine was 171 ± 46 mg, and the duration of drug use was 215 ± 514 days. Hyponatremia occurred in 11 patients (16.2%), and hypokalemia occurred in 8 patients (11.8%). Three patients (4.4%) had hyponatremia and hypokalemia simultaneously. The duration of cicletanine administration was significantly longer in patients with hyponatremia than in those without hyponatremia (943 ± 958 vs. 74 ± 166 days, P < 0.05). The occurrence of hypokalemia was not affected by either daily dose or duration of drug use. Among 11 patients with hyponatremia, 10 were corrected within 2 weeks after withdrawal of the drug and 1 was spontaneously corrected. Among 8 cases of hypokalemia, 7 were corrected after withdrawal of the drug and 1 was spontaneously corrected. CONCLUSION: We demonstrate that cicletanine may induce hyponatremia or hypokalemia in kidney transplant patients. Hyponatremia is more frequently associated with cicletanine than hypokalemia, and extended use of cicletanine may increase the risk of hyponatremia.

A Clinical Study On the Anti-Hypertensive Effect of Cicletanine in Mild to Moderate Hypertensive Patients

BACKGROUND: Cicletanine bydrochloride is a newly developed anti-hypertensive agent. The presence of a furopyridine group characterizes its uncommon chemical structure as an antihypertensive molecule. This clinical trial was performed to confirm the efficacy and safety of cicletanine for the treatment of hypertension as a monotherapy. METHODS: In order to investigate the efficacy and safety of oral cicletanine, a now class of antihypertensive durgs, the furopyridines, on essential hypertension, a single daily dose of 50mg to 100mg cicletanine was administered in 46 hypertensive patients with diastolic blood pressure in the range of 95mmHg-115mmHg. The patients were asked to cut off other anti hypertensive agents for 10 weeks prior to this clinical trial. Blood pressure and heart rate were measured every 4 weeks. The complete blood count, blood chemistry done by SMA-12, serum electrolytes and urinalysis were performed at the 12th week of therapy. RESULTS: 1) Baseline blood pressures after 2 weeks of placebo at sitting and standing positions were 158.7+/-16.1/102.9+/-6.2 and 148.7+/-14.5/102.7+/-6.7mmHg, respectively. The overall slope which represents the tendency of blood pressure decline over the treatment period with cicletanine for all the patients in each position are as follows ; -0.726(SE : 0.150) for sitting systolic blood pressure(BP), -0.390(SE : 0.080) for sitting diastolic BP, -0.214(SE : 0.183) for standing systolic BP and -0.341(SE : 0.139) for standing diastolic BP. 2) The slope of sitting systolic BP line in cicletanine 100mg treated group was significantly stiffer than that of cicletanine 50mg treated group(-0.445 vs -1.021, p=0.0336). 3) There were no significant interval changes in heart rate over the treatment period. 4) There were no significant interval changes in blood chemistry, electrolytes, hematologic findings and urinalysis over the treatment period. 5) Several side effects were observed in six patients(epigastric discomfort in 4, easy fatigue and insomnia in one patient, respectively). CONCLUSION: Treatment with cicletanine was well-tolerated and the incidence of side effects was relatively low. Because of its unique anti-hypertensive mechanism and moderated antihypertensive effects, cicletanine may be well suited in the treatment of hypertension combined with other classes of antihypertensive agents.

A Clinical Study on Cicletanine Monotherapy in Patients with Mild to Moderate Essential Hypertension

BACKGROUND: Cicletanine is a new antihypertensive agent, derived from the furopyridine family. It acts directly on vascular smooth muscle by increasing prostacyclin synthesis and decreasing intracytosolic calcium. In order to investigate the efficacy and safety of cicletanine, a clinical study was performed in the patients with mild to moderate essential hypertension. METHOD: The study subject consisted of 30 patients with diastolic blood pressure of 95mmHg~114mmHg(mean age : 55.1+/-7.9 years, 13 males and 17 females). Cicletanine was administrated orally in a daily dose of 100mg Q.D. for 12 weeks after the administration of a placebo for 2 weeks. During cicletanine medication, antihypertensive efficacy, clinical side effects and laboratory changes were monitored. RESULT: Cicletanine decreased mean blood pressure from the baseline value of 123.6+/-3.4mmHg to 108.6+/-7.5mmHg(p<0.001) after 2 weeks, 105.0+/-7.4mmHg after 4 weeks, 103.9+/-6.6mmHg after 6 weeks, 102.5+/-8.9mmHg after 8 weeks, 101.4+/-6.8mmHg after 10 weeks and 99.6+/-6.6mmHg after 12 weeks of medication. There was a highly significant decrease in blood pressure at each of the assessments after 2,4,6,8,10 and 12 weeks of medication when compared to the baseline value(p<0.001). Mean blood pressure after 4 weeks of medication showed a significant decrease when compared to the value after 2 weeks of medication, and the value after 12 weeks of medication showed a significantly decrease when compared to the value after 8 weeks of medication. Heart rate did not change significantly with cicletanine monotherapy for 12 weeks. There was no significant changes in blood chemistry, glucose, lipid and electrolytes. The side effect was pruritus(1 case, 3.3%). CONCLUSION: Cicletanine monotherapy with 100mg once a day regimen was effective and well tolerated in the patients with mild to moderate essential hypertension.

Inhibitory Effects of Cicletanine and Bepridil on the Contractions of Isolated Rat Thoracic Aorta Rings / 第二军医大学学报

The inhibitory effects of cicletanine (Cic) and bepridil (Bep) on norepinephrine (NE)-and KCl-induced contractions were studied in isolated thoracic aorta rings of male Sprague-Dowley rats. It was found that Cic had a more potent effect on NE-induced contraction than on KCHnduced contraction. In. contrast, Bep had a more potent action on KCHnduced contraction. When the aorta rings were incubated with Cic and Bep, a potentialized inhibitory effect was observed on KCh but not NE-induced contractions. These effects were independent of the presence of endothelium. The results suggest that Cic and Bep have different action sites and properties on vascular smooth muscles.