TY - JOUR
T1 - Responses to intravenous and oral diltiazem in elderly and younger patients with systemic hypertension
AU - Schwartz, Janice B.
AU - Abernethy, Darrell R.
N1 - Funding Information:
From the Baylor College of Medicine, Houston, Texas. This study was supported in part by Grant lK04-00327-01 from the National Institute of Aging, Bethesda, Maryland. Manuscript received October 10, 1986; revised manuscript received and accepted December 8,1986.
PY - 1987/5/1
Y1 - 1987/5/1
N2 - Diltiazem concentrations and blood pressure, heart rate, PR interval and forearm vascular resistance responses to intravenous (25 and 50 mg) and oral (120 mg) diltiazem were compared in 13 elderly persons (mean age 68 ± 4 years) and 10 young persons (mean 30 ± 5 years) with essential hypertension. Diltiazem elimination was slower in the elderly. After a dose of 25 mg, clearance was 13 ± 4 ml/min/kg in the elderly and 23 ± 7 in the young (p < 0.05); after 50 mg, 16 ± 6 and 21 ± 12 ml/ min/kg (p < 0.05); and after oral administration, 22 ± 9 and 35 ± 14 ml/kg/min (p < 0.02). No age-related differences in volume of distribution (by model or area methods) were seen. Elimination half-lives were 4.5 ± 2.2 hours in the elderly and 3.8 ± 0.7 hour in the young persons (p < 0.01); 4.5 ± 1.6 and 3.3 ± 0.7 hours (p = 0.10); and 4.7 ± 1.5 and 3.3 ± 1.8 hours (p = 0.08) after 50, 25 and 120 mg. Maximal decreases in mean blood pressure were from 113 ± 14 to 91 ± 12 mm Hg (19%) in the elderly patients and from 108 ± 8 to 99 ± 9 mm Hg in the younger patients (8%) after 50 mg; from 106 ± 13 to 93 ± 14 mm Hg and from 109 ± 11 to 99 ± 13 mm Hg, respectively, after 25 mg; and from 113 ± 10 to 97 ± 10 mm Hg and from 109 ± 11 to 97 ± 8 after 120 mg orally. Heart rate increased transiently in only the young persons at the end of 50-mg infusions (from 77 ± 14 to 84 ± 8 beats/min, p < 0.05). After oral administration, heart rate decreased significantly in only the elderly (from 75 ± 10 to 65 ± 11 beats/ min at 3 hours after dosing, p < 0.01). Diltiazem (50 mg) produced third-degree heart block in 2 young. No second- or third-degree block occurred in the elderly. After 25-mg infusions, PR interval increased from 170 ± 22 to 219 ± 42 ms in the elderly (p < 0.01) and from 161 ± 12 to 214 ± 29 ms (p < 0.01) in the young patients. After 120 mg, peak increases were from 163 ± 21 to 183 ± 26 ms (p < 0.01) and from 164 ± 24 to 197 ± 27 ms (p < 0.01), respectively. Forearm vascular resistance changed significantly in only the elderly after 25 and 50 mg (from 11.2 ± 3.6 to 10 ± 3.5 U and from 16.6 ± 14 to 13.4 ± 9.5 U, respectively). In summary, slower clearance of diltiazem was found in elderly than in younger hypertensive persons, as were greater hypotensive effects. Reflex heart rate increases were seen in the younger patients and decreases in the elderly. PR prolongation was greater in the younger hypertensive persons.
AB - Diltiazem concentrations and blood pressure, heart rate, PR interval and forearm vascular resistance responses to intravenous (25 and 50 mg) and oral (120 mg) diltiazem were compared in 13 elderly persons (mean age 68 ± 4 years) and 10 young persons (mean 30 ± 5 years) with essential hypertension. Diltiazem elimination was slower in the elderly. After a dose of 25 mg, clearance was 13 ± 4 ml/min/kg in the elderly and 23 ± 7 in the young (p < 0.05); after 50 mg, 16 ± 6 and 21 ± 12 ml/ min/kg (p < 0.05); and after oral administration, 22 ± 9 and 35 ± 14 ml/kg/min (p < 0.02). No age-related differences in volume of distribution (by model or area methods) were seen. Elimination half-lives were 4.5 ± 2.2 hours in the elderly and 3.8 ± 0.7 hour in the young persons (p < 0.01); 4.5 ± 1.6 and 3.3 ± 0.7 hours (p = 0.10); and 4.7 ± 1.5 and 3.3 ± 1.8 hours (p = 0.08) after 50, 25 and 120 mg. Maximal decreases in mean blood pressure were from 113 ± 14 to 91 ± 12 mm Hg (19%) in the elderly patients and from 108 ± 8 to 99 ± 9 mm Hg in the younger patients (8%) after 50 mg; from 106 ± 13 to 93 ± 14 mm Hg and from 109 ± 11 to 99 ± 13 mm Hg, respectively, after 25 mg; and from 113 ± 10 to 97 ± 10 mm Hg and from 109 ± 11 to 97 ± 8 after 120 mg orally. Heart rate increased transiently in only the young persons at the end of 50-mg infusions (from 77 ± 14 to 84 ± 8 beats/min, p < 0.05). After oral administration, heart rate decreased significantly in only the elderly (from 75 ± 10 to 65 ± 11 beats/ min at 3 hours after dosing, p < 0.01). Diltiazem (50 mg) produced third-degree heart block in 2 young. No second- or third-degree block occurred in the elderly. After 25-mg infusions, PR interval increased from 170 ± 22 to 219 ± 42 ms in the elderly (p < 0.01) and from 161 ± 12 to 214 ± 29 ms (p < 0.01) in the young patients. After 120 mg, peak increases were from 163 ± 21 to 183 ± 26 ms (p < 0.01) and from 164 ± 24 to 197 ± 27 ms (p < 0.01), respectively. Forearm vascular resistance changed significantly in only the elderly after 25 and 50 mg (from 11.2 ± 3.6 to 10 ± 3.5 U and from 16.6 ± 14 to 13.4 ± 9.5 U, respectively). In summary, slower clearance of diltiazem was found in elderly than in younger hypertensive persons, as were greater hypotensive effects. Reflex heart rate increases were seen in the younger patients and decreases in the elderly. PR prolongation was greater in the younger hypertensive persons.
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U2 - 10.1016/0002-9149(87)90858-7
DO - 10.1016/0002-9149(87)90858-7
M3 - Article
C2 - 3578052
AN - SCOPUS:0023268239
SN - 0002-9149
VL - 59
SP - 1111
EP - 1117
JO - The American journal of cardiology
JF - The American journal of cardiology
IS - 12
ER -