title: Effect of storage temperature of insulin on pharmacokinetics and pharmacodynamics of insulin mixtures injected subcutaneously in subjects with type 1 (insulin-dependent) diabetes mellitus.
abstract: These studies were undertaken to assess the influence of storage temperature of insulin vials on pharmacokinetics and pharmacodynamics of a mixture of lente insulin (Monotard HM) and regular insulin (Actrapid HM) injected subcutaneously. Seven subjects with Type 1 (insulin-dependent) diabetes mellitus were studied twice after overnight normalization of plasma glucose. A mixture of lente insulin (0.22 U/kg) and regular insulin (0.11 U/kg) was prepared from insulin vials kept either refrigerated (approximately 4 degrees C) or at room temperature (approximately 18 degrees C) and injected subcutaneously (abdomen). Euglycaemia was maintained for the following 16 h by glucose infusion at variable rate. With refrigerated insulin, the plasma free insulin peak was greater (53 +/- 5 versus 45 +/- 6 mU/l) and occurred earlier (2.5 +/- 0.2 versus 6 +/- 0.3 h), and the glucose infusion rate showed a greater (16.5 +/- 1.2 versus 14.5 +/- 0.9 mumol.kg-1.min-1) and earlier peak (3.2 +/- 0.2 versus 6 +/- 0.4 h) as compared to that occurring with the non-refrigerated insulin (p less than 0.05). However, 6 h after insulin injection, both plasma free insulin and glucose infusion rate were 30% lower with the mixture of refrigerated as compared to that of non-refrigerated insulin (p less than 0.05). In contrast, when NPH-insulin (Protaphane HM) was mixed with regular insulin and injected in 4 out of the 7 diabetic patients, the storage temperature of insulin vials had no effect on the pharmacokinetics and pharmacodynamics of the mixture.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Istituto di Patologia Speciale Medica e Metodologia Clinica Università di Perugia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Perriello
authors.forename: E
authors.initials: E
authors.lastname: Torlone
authors.forename: S
authors.initials: S
authors.lastname: Di Santo
authors.forename: C
authors.initials: C
authors.lastname: Fanelli
authors.forename: P
authors.initials: P
authors.lastname: De Feo
authors.forename: F
authors.initials: F
authors.lastname: Santeusanio
authors.forename: P
authors.initials: P
authors.lastname: Brunetti
authors.forename: G B
authors.initials: GB
authors.lastname: Bolli
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D004359:Drug Therapy, Combination; D015309:Glucose Clamp Technique; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D061389:Insulin, Regular, Pork; D013696:Temperature
chemical_list: D007328:Insulin; D049528:Insulin, Long-Acting; D061389:Insulin, Regular, Pork; C000006:insulin, neutral