-
Je něco špatně v tomto záznamu ?
The Effect of Various Degrees of Renal or Hepatic Impairment on the Pharmacokinetic Properties of Once-Weekly Insulin Icodec
H. Haahr, B. Cieslarová, JR. Hingst, S. Jiang, NR. Kristensen, V. Kupčová, L. Nørgreen, FH. Wagner, S. Ignatenko
Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články, klinické zkoušky
NLK
ProQuest Central
od 2007-06-01 do Před 1 rokem
Health & Medicine (ProQuest)
od 2007-06-01 do Před 1 rokem
- MeSH
- dlouhodobě působící inzulin farmakokinetika aplikace a dávkování MeSH
- dospělí MeSH
- hodnoty glomerulární filtrace MeSH
- hypoglykemika * farmakokinetika aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci jater metabolismus MeSH
- renální insuficience metabolismus MeSH
- rozvrh dávkování léků MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
BACKGROUND AND OBJECTIVE: Icodec is a once-weekly insulin being developed to provide basal insulin coverage in diabetes mellitus. This study evaluated the effects of renal or hepatic impairment on icodec pharmacokinetics. METHODS: Two open-label, parallel-group, single-dose (1.5 U/kg subcutaneously) trials were conducted. In a renal impairment trial, 58 individuals were allocated to normal renal function (measured glomerular filtration rate ≥ 90 mL/min), mild (60 to < 90 mL/min), moderate (30 to < 60 mL/min) or severe (< 30 mL/min) renal impairment or end-stage renal disease. In a hepatic impairment trial, 25 individuals were allocated to normal hepatic function or mild (Child-Pugh Classification grade A), moderate (grade B) or severe (grade C) hepatic impairment. Blood was sampled frequently for a pharmacokinetic analysis until 35 days post-dose. RESULTS: The shape of the icodec pharmacokinetic profile was not affected by renal or hepatic impairment. Total icodec exposure was greater for mild (estimated ratio [95% confidence interval]: 1.12 [1.01; 1.24]), moderate (1.24 [1.12; 1.37]) and severe (1.28 [1.16; 1.42]) renal impairment, and for end-stage renal disease (1.14 [1.03; 1.28]), compared with normal renal function. It was also greater for mild (1.13 [1.00; 1.28]) and moderate (1.15 [1.02; 1.29]) hepatic impairment versus normal hepatic function. There was no statistically significant difference between severe hepatic impairment and normal hepatic function. Serum albumin levels (range 2.7-5.1 g/dL) did not statistically significantly influence icodec exposure. CONCLUSIONS: The clinical relevance of the slightly higher icodec exposure with renal or hepatic impairment is limited as icodec should be dosed according to individual need. No specific icodec dose adjustment is required in renal or hepatic impairment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT03723785 and NCT04597697.
Charité Research Organisation Berlin Germany
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc24019991
- 003
- CZ-PrNML
- 005
- 20241024110915.0
- 007
- ta
- 008
- 241015s2024 sz f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1007/s40262-024-01375-2 $2 doi
- 035 __
- $a (PubMed)38722461
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a sz
- 100 1_
- $a Haahr, Hanne $u Novo Nordisk, Søborg, Denmark
- 245 14
- $a The Effect of Various Degrees of Renal or Hepatic Impairment on the Pharmacokinetic Properties of Once-Weekly Insulin Icodec / $c H. Haahr, B. Cieslarová, JR. Hingst, S. Jiang, NR. Kristensen, V. Kupčová, L. Nørgreen, FH. Wagner, S. Ignatenko
- 520 9_
- $a BACKGROUND AND OBJECTIVE: Icodec is a once-weekly insulin being developed to provide basal insulin coverage in diabetes mellitus. This study evaluated the effects of renal or hepatic impairment on icodec pharmacokinetics. METHODS: Two open-label, parallel-group, single-dose (1.5 U/kg subcutaneously) trials were conducted. In a renal impairment trial, 58 individuals were allocated to normal renal function (measured glomerular filtration rate ≥ 90 mL/min), mild (60 to < 90 mL/min), moderate (30 to < 60 mL/min) or severe (< 30 mL/min) renal impairment or end-stage renal disease. In a hepatic impairment trial, 25 individuals were allocated to normal hepatic function or mild (Child-Pugh Classification grade A), moderate (grade B) or severe (grade C) hepatic impairment. Blood was sampled frequently for a pharmacokinetic analysis until 35 days post-dose. RESULTS: The shape of the icodec pharmacokinetic profile was not affected by renal or hepatic impairment. Total icodec exposure was greater for mild (estimated ratio [95% confidence interval]: 1.12 [1.01; 1.24]), moderate (1.24 [1.12; 1.37]) and severe (1.28 [1.16; 1.42]) renal impairment, and for end-stage renal disease (1.14 [1.03; 1.28]), compared with normal renal function. It was also greater for mild (1.13 [1.00; 1.28]) and moderate (1.15 [1.02; 1.29]) hepatic impairment versus normal hepatic function. There was no statistically significant difference between severe hepatic impairment and normal hepatic function. Serum albumin levels (range 2.7-5.1 g/dL) did not statistically significantly influence icodec exposure. CONCLUSIONS: The clinical relevance of the slightly higher icodec exposure with renal or hepatic impairment is limited as icodec should be dosed according to individual need. No specific icodec dose adjustment is required in renal or hepatic impairment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT03723785 and NCT04597697.
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 _2
- $a lidé středního věku $7 D008875
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 _2
- $a senioři $7 D000368
- 650 _2
- $a dospělí $7 D000328
- 650 12
- $a hypoglykemika $x farmakokinetika $x aplikace a dávkování $7 D007004
- 650 _2
- $a nemoci jater $x metabolismus $7 D008107
- 650 _2
- $a dlouhodobě působící inzulin $x farmakokinetika $x aplikace a dávkování $7 D049528
- 650 _2
- $a hodnoty glomerulární filtrace $7 D005919
- 650 _2
- $a rozvrh dávkování léků $7 D004334
- 650 _2
- $a renální insuficience $x metabolismus $7 D051437
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a klinické zkoušky $7 D016430
- 700 1_
- $a Cieslarová, Blanka $u ICON, Prague, Czech Republic
- 700 1_
- $a Hingst, Janne R $u Novo Nordisk, Søborg, Denmark. jrhi@novonordisk.com
- 700 1_
- $a Jiang, Shan $u Novo Nordisk, Shanghai, China
- 700 1_
- $a Kristensen, Niels R $u Novo Nordisk, Søborg, Denmark
- 700 1_
- $a Kupčová, Viera $u Dérer's Hospital, Comenius University, Bratislava, Slovakia
- 700 1_
- $a Nørgreen, Lea $u Novo Nordisk, Aalborg, Denmark
- 700 1_
- $a Wagner, Frank-Dietrich H $u Charité Research Organisation, Berlin, Germany
- 700 1_
- $a Ignatenko, Stanislav $u Charité Research Organisation, Berlin, Germany
- 773 0_
- $w MED00001154 $t Clinical pharmacokinetics $x 1179-1926 $g Roč. 63, č. 6 (2024), s. 819-830
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/38722461 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y - $z 0
- 990 __
- $a 20241015 $b ABA008
- 991 __
- $a 20241024110909 $b ABA008
- 999 __
- $a ok $b bmc $g 2202307 $s 1231964
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2024 $b 63 $c 6 $d 819-830 $e 20240509 $i 1179-1926 $m Clinical pharmacokinetics $n Clin Pharmacokinet $x MED00001154
- LZP __
- $a Pubmed-20241015
