scholarly journals Similar pharmacokinetics and pharmacodynamics of a new biosimilar and reference insulin aspart in healthy Chinese males

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hui Liu ◽  
Hongling Yu ◽  
Lisi Sun ◽  
Jingtao Qiao ◽  
Sainan Wai ◽  
...  
Keyword(s):  
Insulin Aspart ◽  
Area Under The Curve ◽  
Glucose Infusion ◽  
Control Blood Glucose ◽  
Acceptance Limits ◽  
Healthy Chinese ◽  
Total Glucose ◽  
Clamp Study ◽  
To Receive ◽  
Registration Date

AbstractInsulin aspart (IAsp) is one of the main therapies used to control blood glucose after a meal. This study aimed to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of 2 rapid-acting IAsp products: a new IAsp biosimilar (RD10046) and NovoRapid. In a single-center, randomized, single-dose, 2-period, crossover, euglycemic clamp study (registry number: CTR20180517, registration date: 2018-05-30), healthy Chinese males were randomized to receive 0.2 U/kg of the IAsp biosimilar RD10046 and NovoRapid under fasted conditions on two separate occasions. PK and PD were assessed for up to 10 h. Of the 30 randomized subjects, all 30 completed both treatment periods. The PK (area under the curve [AUC] of total IAsp; maximum observed IAsp concentration [Cmax]) and PD (maximum glucose infusion rate [GIRmax]; total glucose infusion during the clamp [AUCGIR,0–10h]) were similar between the new IAsp biosimilar RD10046 and NovoRapid. In all cases, the 90% CIs for the ratios of the geometric means were completely contained in the prespecified acceptance limits of 0.80–1.25. No hypoglycemic events, allergic reactions, or local injection adverse reactions occurred in this trial. We concluded that the studied IAsp biosimilar (RD10046) was bioequivalent to NovoRapid.

scholarly journals Comparison of Pharmacokinetics and Safety of Voriconazole Intravenous-to-Oral Switch in Immunocompromised Adolescents and Healthy Adults

2011 ◽  
Vol 55 (12) ◽  
pp. 5780-5789 ◽  
Author(s):  
Timothy A. Driscoll ◽  
Haydar Frangoul ◽  
Eneida R. Nemecek ◽  
Donald K. Murphey ◽  
Lolie C. Yu ◽  
...  
Keyword(s):  
Body Weight ◽  
Steady State ◽  
Oral Treatment ◽  
Area Under The Curve ◽  
Pharmacokinetic Data ◽  
Young Adolescents ◽  
Dosing Regimens ◽  
Oral Switch ◽  
To Receive ◽  
Higher Doses

ABSTRACTThe current voriconazole dosing recommendation in adolescents is based on limited efficacy and pharmacokinetic data. To confirm the appropriateness of dosing adolescents like adults, a pharmacokinetic study was conducted in 26 immunocompromised adolescents aged 12 to <17 years following intravenous (IV) voriconazole to oral switch regimens: 6 mg/kg IV every 12 h (q12h) on day 1 followed by 4 mg/kg IV q12h, then switched to 300 mg orally q12h. Area under the curve over a 12-hour dosing interval (AUC0–12) was calculated using a noncompartmental method and compared to the value for adults receiving the same dosing regimens. On average, the AUC0–12in adolescents after the first loading dose on day 1 and at steady state during IV treatment were 9.14 and 22.4 μg·h/ml, respectively (approximately 34% and 36% lower, respectively, than values for adults). At steady state during oral treatment, adolescents also had lower average exposure than adults (16.7 versus 34.0 μg·h/ml). Larger intersubject variability was observed in adolescents than in adults. There was a slight trend for some young adolescents with low body weight to have lower voriconazole exposure. It is likely that these young adolescents may metabolize voriconazole more similarly to children than to adults. Overall, with the same dosing regimens, voriconazole exposures in the majority of adolescents were comparable to those in adults. The young adolescents with low body weight during the transitioning period from childhood to adolescence (e.g., 12 to 14 years old) may need to receive higher doses to match the adult exposures. Safety of voriconazole in adolescents was consistent with the known safety profile of voriconazole.

scholarly journals Influence of Cytochrome P450 2C19 on the pharmacokinetics of lansoprazole administered by single and successive intravenous infusion in healthy Chinese volunteers

2012 ◽  
Vol 2 (1) ◽  
pp. 3 ◽  
Author(s):  
Yongqing Wang ◽  
Peipei Zhang ◽  
Ningling Jiang ◽  
Xiaojian Gong ◽  
Dewang Wang ◽  
...  
Keyword(s):  
Intravenous Infusion ◽  
High Performance ◽  
Dose Range ◽  
Plasma Concentrations ◽  
Linear Increase ◽  
Cytochrome P450 2C19 ◽  
Repeated Doses ◽  
Healthy Chinese ◽  
To Receive ◽  
Single Intravenous Infusion

This study aimed to explore the effect of CYP2C19 polymorphisms on the pharmacokinetics of lansoprazole administered by single and successive intravenous (iv) infusions in healthy Chinese volunteers. A total of 30 subjects, including 20 extensive metabolizers (EMs) and 10 poor metabolizers (PMs) were recruited and randomly assigned to three groups receiving doses of 15, 30 and 60 mg. All subjects received a single dose of lansoprazole during a 60-min period, and only the 30 mg dose group continued to receive the same dose iv for the next seven days (twice daily). Plasma concentrations of lansoprazole were monitored by high performance liquid chromatography (HPLC) at the following times: 15, 30, 45, 60, 75, 105, 165, 225, 300, 390, 480, 600 and 720 min after lansoprazole administration. After a single intravenous infusion in the three groups, AUC, Cmax and t½ were significantly higher in PMs than in EMs, while total clearance (Cltotal) in PMs was significantly lower than that in EMs. Mean AUC and Cmax ratios in EMs and PMs were 2.1:1 and 1.4:1, respectively. After repeated doses of 30 mg, the AUC, Cmax, and t½ increased significantly, while the Cltotal decreased significantly in EMs. Mean AUC and Cmax ratios in EMs and PMs amounted to 2.2:1.4 and 1.5:1.2, respectively. Lansoprazole displays a linear increase in AUC and Cmax over a dose range of 15-60 mg, and these were dependent on individual CYP2C19 status.

Preexercise muscle glycogen content affects metabolism during exercise despite maintenance of hyperglycemia

1998 ◽  
Vol 274 (1) ◽  
pp. E83-E88 ◽  
Author(s):  
Sandra M. Weltan ◽  
Andrew N. Bosch ◽  
Steven C. Dennis ◽  
Timothy D. Noakes
Keyword(s):  
Muscle Glycogen ◽  
Glucose Oxidation ◽  
Glycogen Content ◽  
Respiratory Exchange Ratio ◽  
Glucose Infusion ◽  
Muscle Glycogen Content ◽  
Hyperglycemic Clamp ◽  
Upper Limit ◽  
Glycogen Utilization ◽  
Total Glucose

Trained cyclists with low muscle glycogen (LGH; n = 8) or normal glycogen (NGH; n = 5) exercised for 145 min at 70% of maximal oxygen uptake during a hyperglycemic clamp. Respiratory exchange ratio was higher in NGH than LGH, and free fatty acid concentrations were lower in NGH than LGH. Areas under the curve for insulin and lactate were lower in LGH than NGH. Total glucose infusion and total glucose oxidation were not different between NGH and LGH, and total glucose oxidation amounted to 65 and 66% of total glucose infusion in NGH and LGH, respectively. Rates of glucose oxidation rose during exercise, reaching peaks of 9.2 ± 1.7 and 8.3 ± 1.1 mmol/min in NGH and LGH, respectively. Muscle glycogen disappearance was greater in NGH than LGH. Thus 1) low muscle glycogen content does not cause increased glucose oxidation, even during hyperglycemia; instead there is an increase in fat oxidation, 2) there is an upper limit to the rate of glucose oxidation during exercise with hyperglycemia irrespective of muscle glycogen status, and 3) net muscle glycogen utilization is determined by muscle glycogen content at the start of exercise, even during hyperglycemia.

No accumulation of glucose in human skeletal muscle during euglycemic hyperinsulinemia

1988 ◽  
Vol 255 (6) ◽  
pp. E942-E945 ◽  
Author(s):  
A. Katz ◽  
B. L. Nyomba ◽  
C. Bogardus
Keyword(s):  
Skeletal Muscle ◽  
Glucose Concentration ◽  
Human Skeletal Muscle ◽  
Dry Weight ◽  
Glucose Infusion ◽  
High Dose ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Glucose Content ◽  
Free Glucose ◽  
Total Glucose

It has been recently suggested that high glucose infusion rates during euglycemic hyperinsulinemia result in accumulation of free glucose in human skeletal muscle (J. Clin. Invest. 76: 357, 1985). To examine this possibility, we performed a euglycemic, hyperinsulinemic clamp together with biopsies from the quadriceps femoris muscle on seven healthy men. Insulin was infused at successive rates of 40 and 400 mU. m-2.min-1, resulting in mean plasma insulin concentrations of 69 +/- 3 and 1,285 +/- 115 (SE) microU/ml, respectively. Glucose infusion rates averaged 7.79 +/- 0.86 and 12.01 +/- 0.77 mg.kg body wt-1.min-1. The total glucose content in muscle averaged 1.72 +/- 0.26, 1.37 +/- 0.21, and 1.65 +/- 0.35 mmol/kg dry wt at rest, and after the low- and high-dose insulin infusions, respectively (P greater than 0.05). Assuming that the plasma glucose concentration reflects the glucose concentration in the extracellular space and that there are 0.3 liters of extracellular water per kilogram dry weight, the intracellular glucose contents are calculated to be 0.15 +/- 0.25, -0.35 +/- 0.21, and -0.06 +/- 0.34 mmol/kg dry wt at rest, and after the low- and high-dose infusions, respectively. None of these values is significantly different from zero. Thus euglycemic hyperinsulinemia does not result in appreciable accumulation of glucose in the muscle of insulin-sensitive men.

A randomized, crossover phase I study to assess the effects of formulation and meal consumption on the bioavailability of dovitinib (TKI258).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2593-2593 ◽  
Author(s):  
Sunil Sharma ◽  
Ramesh K. Ramanathan ◽  
Daniel J. George ◽  
Michelle Quinlan ◽  
Swarupa Kulkarni ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Geometric Mean ◽  
Area Under The Curve ◽  
Relative Bioavailability ◽  
Crossover Designs ◽  
Once Daily ◽  
Relevant Effect ◽  
Crossover Phase ◽  
Effect Of Food ◽  
To Receive

2593 Background: Dovitinib (TKI258), an oral multitargeted receptor tyrosine kinase inhibitor, is being studied in a phase 3 trial for renal cell carcinoma. A previous study compared the bioavailability of 2 capsule formulations of dovitinib. Arm 1 of the current study compared relative bioavailability of the final market image (FMI) form (monohydrate tablets) with the clinical service form (CSF; anhydrate capsules) of dovitinib. Arm 2 assessed the effect of food on bioavailability of the FMI tablet in adult patients (pts) with advanced solid tumors. Both arms employed crossover designs. Methods: In arm 1, pts were randomized to receive a single 500-mg dose of dovitinib either as a CSF capsule or FMI tablet, followed by a single 500-mg dose of the other formulation after 7 days of rest. Plasma pharmacokinetic (PK) profiles were determined from blood samples. A linear mixed-effects model fitted to log-transformed PK parameters maximal concentration (Cmax) and area under the curve (AUC0-tlast) was used to determine the relative bioavailability of FMI vs CSF. In Arm 2, pts received 300 mg of the FMI formulation once daily for 22 days after being randomized to 1 of 6 meal sequences with 3 fed or nonfed states (no meal [NM], low-fat [LF] meal, or high-fat [HF] meal) on days 8, 15, and 22. The relative bioavailability of dovitinib under LF and HF vs NM state was determined using the same model as arm 1 for the PK parameters Cmax and AUC0-tlast. Results: The study accrued 21 pts to arm 1 and 42 pts to arm 2. Based on the interim analysis, PK was assessed in 17 evaluable pts in arm 1. The geometric mean ratios (GMRs; 90% CI) for Cmax and AUC0-tlast comparing FMI vs CSF were 0.99 (0.91-1.08) and 0.96 (0.89-1.04), respectively. The FMI formulation was used in arm 2; PK was assessed in 19 pts. Cmax GMR (90% CI) was 0.82 (0.71-0.94) and 0.90 (0.78-1.03) for HF/NM and LF/NM, respectively. AUC0-tlastGMR (90% CI) was 0.91 (0.81-1.02) and 0.99 (0.88-1.10) for HF/NM and LF/NM, respectively. Conclusions: The oral bioavailability of the FMI tablet and CSF capsule were comparable, and there was no clinically relevant effect of food (HF or LF meals) on the bioavailability of the FMI tablet form of dovitinib. Clinical trial information: NCT01155713.

Sign in / Sign up

Export Citation Format

Share Document