Abstract：
:X-linked hypophosphatemia (XLH) is an inherited metabolic bone disease with abnormally elevated serum FGF23 resulting in low renal maximum threshold for phosphate reabsorption, low serum phosphate (Pi) and 1,25-dihydroxyvitamin D levels with subsequent development of short stature and skeletal deformities. KRN23 is a novel human anti-FGF23 antibody for the treatment of XLH. The pharmacokinetics (PK) and pharmacodynamics (PD) models of KRN23 were assessed following subcutaneous dosing every 28 days over an initial 4-month dose escalation (0.05-0.6 mg/kg) and a subsequent 12-month titration period (0.1-1.0 mg/kg) in XLH adults. The PK of KRN23 was described by a 1-compartmental model with first-order absorption and elimination at doses ≥0.1 mg/kg. The elimination half-life was 17.8 days. Covariates did not affect KRN23 PK. Mean peak serum Pi was attained 7-10 days after dosing and progressively increased following each of the initial 4 doses with comparable peak values attained following the sixth through tenth doses with a slight decrease thereafter. A PK-PD model with a maximum effect (Emax ) and a time-varying effective concentration to reach 50% of Emax (EC50,t ) described data adequately. Typical Emax was 1.5 mg/dL. Typical EC50,t was 1780 ng/mL and 5999 ng/mL after first and last dose, respectively.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Zhang X,Peyret T,Gosselin NH,Marier JF,Imel EA,Carpenter TOdoi
10.1002/jcph.611subject
Has Abstractpub_date
2016-04-01 00:00:00pages
429-38issue
4eissn
0091-2700issn
1552-4604journal_volume
56pub_type
杂志文章abstract：:The hypotensive efficacy of labetalol was evaluated in 29 patients with essential hypertension in a single-blind dose ranging study. After a two-week period of placebo treatment, labetalol was given in oral doses of 0.6 g/d, 0.8 g/d, and 0.8 g/d combined with 25-50 mg/d of hydrochlorothiazide. Each regimen lasted four...
journal_title：Journal of clinical pharmacology
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pub_type： 杂志文章,随机对照试验
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1981.tb02611.x
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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pub_type： 临床试验,杂志文章,随机对照试验
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pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
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journal_title：Journal of clinical pharmacology
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