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@#We present a case of a 27-year-old female with T2 DM who developed allergic reactions after commencement of insulin therapy. Trial with different types of insulin resulted in a series of allergic reactions ranging from urticarial rash to development of angioedema, bronchospasm and anaphylactic shock. She was successfully treated with a modified insulin desensitization protocol using rapid-acting insulin.
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ExcipientsABSTRACT
Objective To study the pharmacokinetics and pharmacodynamics of the 40/60 premixed recombinant human insulin injection preparation,and to compare with 30/70 preparation,regular insulin,and neutral protamine Hagedorn (NPH).Methods In this positive control,single dose,open label,Latin square crossover study,20 male healthy volunteers were recruited from May 2006 to March 2007,and divided into four groups.On 4 test days,40/60 preparation,30/70 preparation,regular insulin,and NPH were administered to each of the 4 groups,the interval was 7-70 days before 2 test days.The pharmacokinetics and pharmacodynamics were evaluated by euglycemic glucose clamp technique.Results According to the analysis of variance,there were statistically significant differences in pharmacokinetics and pharmacodynamics of the 4 insulin formulations between the 4 groups (all P ＜ 0.05).For the 40/60 premixed recombinant human insulin,the pharmacokinetic parameter time to peak (Tmax) and mean retention time (MRT) were (105.00 ±24.33) minutes and (321.77 ± 56.29) minutes,respectively;the glucose-lowering effects reflected by the pharmacodynamic parameter Tmax and MRT were (167.75 ± 26.48) minutes and (248.33 ± 14.96) minutes,respectively.Compared with 30/70 premixed recombinant human insulin,40/60 preparation showed no significant differences in the pharmacokinetics parameters of blood insulin concentration,including peak concentration [(91.67 ± 13.03) mU/L vs.(84.96 ± 14.75) mU/L,P =0.119],Tmax [(105.00 ± 24.33) minutes vs.(122.25 ± 39.35) minutes,P =0.128],MRT [(321.77 ± 56.29) minutes vs.(332.12 ± 49.20) minutes,P =0.645] and area under the curve in 0-16 hours [AUCIns 0-16,(24 918 ± 6 610)h · mU/L vs.(26 768 ± 8 032)h· mU/L,P=0.084];however,statistically significant differences were observed in AUCIns0-4 [(16 991 ± 3 673) h · mU/L vs.(12 407 ± 3 441) h · mU/L,P =0.042] and AUCIns 0-8 [(23 283 ± 4 939) h · mU/L vs.(19 397 ±5 314)h · mU/L,P =0.046].Pharmacodynamic parameters showed no statistically significant differences (all P ＞ 0.05).Compared with 30/70 premixed insulin,the relative bioavailability of 40/60 premixed insulin was (118.9 ± 35.9) ％,and the relative biological effectiveness was (106.6 ± 35.2) ％.There was no clinically significant abnormalities in the safety indexes before and after the tests.No hypoglycemic events,allergic reactions,or local injection adverse reaction occurred in this trial.Conclusions The 40/60 premixed recombinant human insulin preparation demonstrated different properties in insulin absorption in 8 hours after injection compared with the 30/70 preparation,mainly because of the difference in proportions of short-and intermediate-acting insulin in the mixture.This new premixed insulin may provide a new option for personalized diabetes management.
ABSTRACT
Objective To study the pharmacokinetics and pharmacodynamics of recombinant human insulin preparations SciLin TM R and Humulin (R) R,and to evaluate their bioequivalence in Chinese healthy volunteers.Methods In this positive control,single dose,open label,randomized cross-over study,20 male healthy volunteers were recruited from March to October 2007,and tested on two experimental days with an interval of 7-14 days.The volunteers were divided into two groups with a random number table,one group was injected with SciLin TMR for the first time and Humulin (R) R for the second time,the other group was injected with the opposite.The pharmacokinetics and pharmacodynamic properties were evaluated by euglycemic glucose clamp study.Results Time to peak concentration [Tmax,(105.8 ± 19.1) minutes vs.(103.5 ± 18.1) minutes,P =0.389) and time to maximum glucose infusion rate [TGIRmax,(132.8 ± 16.8) minutes vs.(132.8 ± 18.6) minutes,P =0.697] for SciLin TMR and Humulin(R) R were similar.The relative bioavailability of SciLin TMR was (102.2 ± 7.6) ％,and the relative biological effectiveness was (107.4 ± 18.8) ％.The 90％ confidence interval(CI) of peak concentration(Cmax) and area under the curve of blood glucose concentration at 0-10 hours (AUCIns 0-10) of SciLin TM R were 99.32 ％-102.62 ％ (equivalent range 70％-143 ％) and 98.98 ％-104.99 ％ (equivalent range 80％-125％),respectively;90％ CI of the maximum glucose infusion rate (GIRmax) and AUCGIR0-10 were 97.36％ ～ 103.49％ (equivalent range 70％-143％) and 98.72％-113.54％ (equivalent range 80％-125％),respectively,indicating that SciLin TMR and Humulin (R) R was bioequivalent.There was no clinically significant abnormalities in the safety indexes before and after the tests.During the trial,no hypoglycemic events,allergic reactions,or local injection adverse reaction occurred.Conclusion The studied recombinant human insulin preparation SciLin TMR may be bioequivalent as Humulin (R) R.
