Captopril-induced creatine kinase elevations: a possible role of the sulfhydryl group.

Since captopril, the first orally active angiotensin converting enzyme inhibitor, was introduced into clinical medicine, this new approach to blocking the formation of angiotensin II and lowering the blood pressure, appears to be tolerated well in most hyperten-sive patients. 1 However, during a randomized trial comparing the antihypertensive efficacy of captopril, 25 mg b.i.d., with captopril, 25 mg t.i.d., we found elevated creatine kinase (CK; EC 2.7.3.2) levels in several patients. In the present study, therefore, CK levels in 44 patients with mild to moderate hyperten-sion (24 men and 20 women; average age, 53.5 ± 2.0 [S.E.] years) treated with captopril were reviewed retrospectively. Thirty of these patients were treated with captopril alone, while 14 were treated with captopril in addition to other hypotensive agents: diuretics in eight, /3-blockers (atenolol) in two, diuretics with /3-blockade in three (atenolol in one, propranolol in two) and nifedipine in one. The duration of treatment ranged from 1 to 26 months. The average captopril dosage was 60.7 mg/day and ranged from 25 to 75 mg/day. (Unless otherwise specified, all data are expressed as means ± SE.) Blood pressure declined significantly from 167 ± respectively, of captopril administration. Before treatment with captopril, three of the 44 patients had a CK value that exceeded our hospital's normal range (11-136 IU/L). In the remaining 41 patients , CK activities were determined 47 times before and 161 times after treatment. Captopril administration significantly elevated CK activities from 71.9 ± 4.3 to 84.7 ± 3.3 IU/L (/><0.05). When reanalyzed according to the dosage of captopril, the average CK levels were 82.2 ± 3.7 (w = 56 determinations, NS) at 25 to 37.5 mg/day and 86.0 ± 4.6 IU/L (n = 105 deter-minations, p<0.05) at 50 to 75 mg/day. As a result, 20 CK determinations in six patients exceeded their pretreatment mean + 2 SD of 131.5 IU/L. The time course of CK values in five of these six hypertensive patients is illustrated in Figure 1. On the other hand, in one (Patient 7 in Figure 1) of three patients with a high initial CK level, combined treatment with captopril, 75 mg/day, and indapamide, 1 mg/day, resulted in a further , progressive, 3-month rise in CK (from 143 to 179 to 300 to 334 IU/L) followed by normalization of CK activity 1 month after drug administration was stopped. One month later, captopril challenge at 50 mg/day again increased CK activity …