To compare the pharmacokinetics/dynamics of the long- acting insulin analog glargine with NPH, ultralente, and continuous subcutaneous (SC) infusion of insulin lispro (continuous subcutaneous insulin infusion [CSII]), 20 C-peptide–negative type 1 diabetic patients were stud- ied on four occasions during an isoglycemic 24-h clamp. Patients received SC injection of either 0.3 U/kg glargine or NPH insulin (random sequence, crossover design). On two subsequent occasions, they received either an SC injection of ultralente (0.3 U/kg) or CSII (0.3 U · kg–1 · 24 h–1) (random sequence, crossover design). After SC insulin injection or CSII, intravenous (IV) insulin was tapered, and glucose was infused to clamp plasma glucose at 130 mg/dl for 24 h. Onset of action (defined as reduction of IV insulin >50%) was ear- lier with NPH (0.8 ± 0.2 h), CSII (0.5 ± 0.1 h), and ultra- lente (1 ± 0.2 h) versus glargine (1.5 ± 0.3 h) (P < 0.05) (mean ± SE). End of action (defined as an increase in plasma glucose >150 mg/dl) occurred later with glargine (22 ± 4 h) than with NPH (14 ± 3 h) (P < 0.05) but was similar with ultralente (20 ± 6 h). NPH and ultralente exhibited a peak concentration and action (at 4.5 ± 0.5 and 10.1 ± 1 h, respectively) followed by waning, whereas glargine had no peak but had a flat concentra- tion/action profile mimicking CSII. Interindividual vari- ability (calculated as differences in SD of plasma insulin concentrations and glucose infusion rates in dif- ferent treatments) was lower with glargine than with NPH and ultralente (P < 0.05) but was similar with glargine and CSII (NS). In conclusion, NPH and ultra- lente are both peak insulins. Duration of action of ultralente is greater, but intersubject variability is also greater than that of NPH. Glargine is a peakless insulin, it lasts nearly 24 h, it has lower intersubject variability than NPH and ultralente, and it closely mim- ics CSII, the gold standard of basal insulin replacement

Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro

FANELLI, Carmine Giuseppe;PORCELLATI, Francesca;BRUNETTI, Paolo;BOLLI, Geremia Brunetto
2000

Abstract

To compare the pharmacokinetics/dynamics of the long- acting insulin analog glargine with NPH, ultralente, and continuous subcutaneous (SC) infusion of insulin lispro (continuous subcutaneous insulin infusion [CSII]), 20 C-peptide–negative type 1 diabetic patients were stud- ied on four occasions during an isoglycemic 24-h clamp. Patients received SC injection of either 0.3 U/kg glargine or NPH insulin (random sequence, crossover design). On two subsequent occasions, they received either an SC injection of ultralente (0.3 U/kg) or CSII (0.3 U · kg–1 · 24 h–1) (random sequence, crossover design). After SC insulin injection or CSII, intravenous (IV) insulin was tapered, and glucose was infused to clamp plasma glucose at 130 mg/dl for 24 h. Onset of action (defined as reduction of IV insulin >50%) was ear- lier with NPH (0.8 ± 0.2 h), CSII (0.5 ± 0.1 h), and ultra- lente (1 ± 0.2 h) versus glargine (1.5 ± 0.3 h) (P < 0.05) (mean ± SE). End of action (defined as an increase in plasma glucose >150 mg/dl) occurred later with glargine (22 ± 4 h) than with NPH (14 ± 3 h) (P < 0.05) but was similar with ultralente (20 ± 6 h). NPH and ultralente exhibited a peak concentration and action (at 4.5 ± 0.5 and 10.1 ± 1 h, respectively) followed by waning, whereas glargine had no peak but had a flat concentra- tion/action profile mimicking CSII. Interindividual vari- ability (calculated as differences in SD of plasma insulin concentrations and glucose infusion rates in dif- ferent treatments) was lower with glargine than with NPH and ultralente (P < 0.05) but was similar with glargine and CSII (NS). In conclusion, NPH and ultra- lente are both peak insulins. Duration of action of ultralente is greater, but intersubject variability is also greater than that of NPH. Glargine is a peakless insulin, it lasts nearly 24 h, it has lower intersubject variability than NPH and ultralente, and it closely mim- ics CSII, the gold standard of basal insulin replacement
2000
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11391/1039058
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