Abstract
Tolrestat is an aldose reductase inhibitor undergoing clinical trials in diabetic subjects that may reduce the severity of chronic tissue damage associated with hyperglycemia. These studies were conducted to evaluate the pharmacokinetics of tolrestat in healthy young and elderly male and female subjects and in young and elderly subjects with diabetes. The drug was administered in a multiple-dose regimen, and steady-state parameters were obtained. There were no important gender-related differences, but mean values for apparent oral clearance, renal clearance, and corresponding unbound parameters were significantly lower for the elderly healthy subjects than for the young healthy subjects. The drug is highly bound to plasma proteins, and the unbound fraction (0.75%) did not differ among the subjects. The results from young and elderly diabetic subjects suggest. that diabetes per se has no influence on tolrestat disposition but that there is an age-related reduction in apparent oral clearance (30 versus 18 ml/hr/kg) and a corresponding increase in the minimum steady-state plasma concentration (1.2 versus 1.9 μg/ml). These data indicate a possible need to reduce the dose of tolrestat in elderly subjects, assuming the same concentration-response relationship.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 603-612 |
| Number of pages | 10 |
| Journal | Clinical Pharmacology and Therapeutics |
| Volume | 59 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1996 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Pharmacology
Cite this
Pharmacokinetics of the aldose reductase inhibitor tolrestat : Studies in healthy young and elderly male and female subjects and in subjects with diabetes. / Fruncillo, Richard; Troy, Steven; Parker, Vernon; Mayersohn, Michael; Hicks, David; Kraml, Michael; Battle, Michele; Chiang, Soong.
In: Clinical Pharmacology and Therapeutics, Vol. 59, No. 6, 06.1996, p. 603-612.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pharmacokinetics of the aldose reductase inhibitor tolrestat
T2 - Studies in healthy young and elderly male and female subjects and in subjects with diabetes
AU - Fruncillo, Richard
AU - Troy, Steven
AU - Parker, Vernon
AU - Mayersohn, Michael
AU - Hicks, David
AU - Kraml, Michael
AU - Battle, Michele
AU - Chiang, Soong
PY - 1996/6
Y1 - 1996/6
N2 - Tolrestat is an aldose reductase inhibitor undergoing clinical trials in diabetic subjects that may reduce the severity of chronic tissue damage associated with hyperglycemia. These studies were conducted to evaluate the pharmacokinetics of tolrestat in healthy young and elderly male and female subjects and in young and elderly subjects with diabetes. The drug was administered in a multiple-dose regimen, and steady-state parameters were obtained. There were no important gender-related differences, but mean values for apparent oral clearance, renal clearance, and corresponding unbound parameters were significantly lower for the elderly healthy subjects than for the young healthy subjects. The drug is highly bound to plasma proteins, and the unbound fraction (0.75%) did not differ among the subjects. The results from young and elderly diabetic subjects suggest. that diabetes per se has no influence on tolrestat disposition but that there is an age-related reduction in apparent oral clearance (30 versus 18 ml/hr/kg) and a corresponding increase in the minimum steady-state plasma concentration (1.2 versus 1.9 μg/ml). These data indicate a possible need to reduce the dose of tolrestat in elderly subjects, assuming the same concentration-response relationship.
AB - Tolrestat is an aldose reductase inhibitor undergoing clinical trials in diabetic subjects that may reduce the severity of chronic tissue damage associated with hyperglycemia. These studies were conducted to evaluate the pharmacokinetics of tolrestat in healthy young and elderly male and female subjects and in young and elderly subjects with diabetes. The drug was administered in a multiple-dose regimen, and steady-state parameters were obtained. There were no important gender-related differences, but mean values for apparent oral clearance, renal clearance, and corresponding unbound parameters were significantly lower for the elderly healthy subjects than for the young healthy subjects. The drug is highly bound to plasma proteins, and the unbound fraction (0.75%) did not differ among the subjects. The results from young and elderly diabetic subjects suggest. that diabetes per se has no influence on tolrestat disposition but that there is an age-related reduction in apparent oral clearance (30 versus 18 ml/hr/kg) and a corresponding increase in the minimum steady-state plasma concentration (1.2 versus 1.9 μg/ml). These data indicate a possible need to reduce the dose of tolrestat in elderly subjects, assuming the same concentration-response relationship.
UR - http://www.scopus.com/inward/record.url?scp=0030017101&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030017101&partnerID=8YFLogxK
U2 - 10.1016/S0009-9236(96)90000-4
DO - 10.1016/S0009-9236(96)90000-4
M3 - Article
C2 - 8681485
AN - SCOPUS:0030017101
VL - 59
SP - 603
EP - 612
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
SN - 0009-9236
IS - 6
ER -