OBJECTIVEHuman regular U-500 (U-500R) insulin (500 units/mL) is increasingly being used clinically, yet its pharmacokinetics (PK) and pharmacodynamics (PD) have not been well studied. Therefore, we compared PK and PD of clinically relevant doses of U-500R with the same doses of human regular U-100 (U-100R) insulin (100 units/mL).RESEARCH DESIGN AND METHODSThis was a single-site, randomized, double-blind, crossover euglycemic clamp study. Single subcutaneous injections of 50- and 100-unit doses of U-500R and U-100R were administered to 24 healthy obese subjects.RESULTSBoth overall insulin exposure (area under the serum insulin concentration versus time curve from zero to return to baseline [AUC0-t’]) and overall effect (total glucose infused during a clamp) were similar between formulations at both 50- and 100-unit doses (90% [CI] of ratios contained within [0.80, 1.25]). However, peak concentration and effect were significantly lower for U-500R at both doses (P < 0.05). Both formulations produced relatively long durations of action (18.3 to 21.5 h). Time-to-peak concentration and time to maximum effect were significantly longer for U-500R than U-100R at the 100-unit dose (P < 0.05). Time variables reflective of duration of action (late tRmax50, tRlast) were prolonged for U-500R versus U-100R at both doses (P < 0.05).CONCLUSIONSOverall exposure to and action of U-500R insulin after subcutaneous injection were no different from those of U-100R insulin. For U-500R, peaks of concentration and action profiles were blunted and the effect after the peak was prolonged. These findings may help guide therapy with U-500R insulin for highly insulin-resistant patients with diabetes.
Insulin lispro 200 U/mL (IL200) is a new strength formulation of insulin lispro (Humalog®, IL100), developed as an option for diabetic patients on higher daily mealtime insulin doses. This phase 1, open‐label, 2‐sequence, 4‐period crossover, randomized, 8‐hour euglycemic clamp study aimed to demonstrate the bioequivalence of IL200 and IL100 after subcutaneous administration of 20 U (U) to healthy subjects (n = 38). Pharmacokinetic (PK) and pharmacodynamic (PD) responses were similar in both formulations. All 90%CIs for the ratios of area under the concentration‐versus‐time curve from time zero to the time of the last measurable concentration (AUC0–tlast) and maximum observed drug concentration (Cmax), as well as the total glucose infused throughout the clamp (Gtot) and the maximum glucose infusion rate (Rmax), were contained within 0.80 and 1.25. Time of maximum observed drug concentration (tmax) was similar between formulations, with a median difference of 15 minutes and a 95%CI of the difference that included zero. Inter‐ and intrasubject variability estimates were similar for both formulations. Both formulations were well tolerated. IL200 was bioequivalent to IL100 after subcutaneous administration of 20‐U single doses, and PD responses were comparable between formulation strengths.
Content and FocusThis paper seeks to answer the following question: ‘How can a pluralistic therapist use a single school approach and remain faithful to their philosophical and collaborative base?’ To do this it explores some of the difficulties associated with integrative/eclectic approaches to therapy. Within this it discusses pluralistic philosophy and suggests that the proverb ‘there is more than one way to skin a cat’ is a helpful way of summarising pluralistic philosophy. From there it discusses Cooper and McLeod’s (2011) Pluralistic Framework for counselling and psychotherapy as an integrative approach and focuses on two distinguishing elements of it; namely that it has its basis in pluralistic philosophy rather than psychological theory and that it is collaborative in nature. The discussion then turns towards mindfulness-based cognitive therapy (MBCT) and the theory and research evidence that underpins it with a view to considering how a single school approach may fit with a pluralist approach. The paper reflects upon two opposing answers to the dilemma that is inherent within the question referred to at the outset of this abstract, suggesting rationale both for and against the use of MBCT from a pluralistic position.ConclusionThe paper concludes by offering the concept of Pragmatic Pluralism as a way for pluralistic therapists to undergird their therapeutic decision making.
In the Supplementary Data of the article cited above, there is an error in Supplementary Fig. 2. The data point label for tR max (beneath the x-axis) "tR max 5 time of half-maximum GIR" should read "tR max 5 time of maximum GIR." In addition, the block blue color that fills the area under the curve should not extend beyond the x-axis. The corrected Supplementary Fig. 2 appears below. The online version reflects these changes.
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