PMID- 19947907
OWN - NLM
STAT- MEDLINE
DCOM- 20100430
LR  - 20190828
IS  - 1473-4877 (Electronic)
IS  - 0300-7995 (Linking)
VI  - 26
IP  - 2
DP  - 2010 Feb
TI  - Safety and pharmacokinetics of subcutaneous ceftriaxone administered with or 
      without recombinant human hyaluronidase (rHuPH20) versus intravenous ceftriaxone 
      administration in adult volunteers.
PG  - 279-88
LID - 10.1185/03007990903432900 [doi]
AB  - OBJECTIVE: To compare pharmacokinetics and safety of recombinant human 
      hyaluronidase (rHuPH20)-facilitated subcutaneous (SC) ceftriaxone administration 
      versus SC ceftriaxone preceded by SC saline placebo or intravenous (IV) 
      ceftriaxone administration. RESEARCH DESIGN AND METHODS: This Phase I, two-part, 
      placebo-controlled, crossover study was conducted in 54 healthy volunteers. In 
      Part 1 (N = 24), subjects received 1 mL rHuPH20 (150 USP units) or placebo (0.9% 
      sodium chloride) SC, followed by 1 or 2 g ceftriaxone (10-350 mg/mL). In Part 2 
      (N = 30), subjects received 1 g ceftriaxone at the Part 1 maximum tolerated 
      concentration (MTC) administered either SC - preceded by SC rHuPH20 or placebo - 
      or IV. Subjects were monitored for adverse events (AEs); blood samples were 
      obtained (Part 2 only) during 48 hours post-dosing for ceftriaxone bioanalysis. 
      MAIN OUTCOME MEASURES: Part 1 primary endpoint was the SC ceftriaxone (with or 
      without rHuPH20) MTC. Pharmacokinetic parameters were determined in Part 2. 
      Bioequivalence was based on maximum concentration (C(max)) and area under plasma 
      concentration-time curve (AUC). RESULTS: The highest SC ceftriaxone concentration 
      tested in Part 1 (350 mg/mL) was selected as the Part 2 MTC. In Part 2, median 
      time to maximum concentration (t(max)) was 1 hour earlier (P < 0.0001), and 
      C(max) was 12% higher (P < 0.0001) for ceftriaxone (350 mg/mL) administered via 
      rHuPH20-facilitated SC versus SC preceded by placebo. IV ceftriaxone led to 
      higher C(max) and shorter t(max) values than either SC treatment. Ceftriaxone 
      exposure (AUC) was comparable among all three treatments. At least 1 AE was 
      experienced by 100% of subjects after SC ceftriaxone and 76% after IV; most 
      commonly reported AEs were infusion-site reactions. CONCLUSIONS: Ceftriaxone AUC 
      did not differ significantly between the three administration routes. C(max) was 
      higher and t(max) shorter with rHuPH20-facilitated SC than SC preceded by 
      placebo. rHuPH20-facilitated SC ceftriaxone was generally well tolerated. This 
      study is limited by evaluation of healthy adults and absence of repeated-dose 
      groups.
FAU - Harb, George
AU  - Harb G
AD  - Baxter Healthcare Corporation, Deerfield, IL, USA. george harb@baxter.com
FAU - Lebel, Francois
AU  - Lebel F
FAU - Battikha, Jean
AU  - Battikha J
FAU - Thackara, Jeffrey W
AU  - Thackara JW
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Med Res Opin
JT  - Current medical research and opinion
JID - 0351014
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Placebos)
RN  - 0 (Recombinant Proteins)
RN  - 75J73V1629 (Ceftriaxone)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 3.2.1.169 (OGA protein, human)
RN  - EC 3.2.1.35 (Hyaluronoglucosaminidase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antigens, Neoplasm/*administration & dosage/adverse effects
MH  - Ceftriaxone/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Histone Acetyltransferases/*administration & dosage/adverse 
      effects/*pharmacokinetics
MH  - Humans
MH  - Hyaluronoglucosaminidase/*administration & dosage/adverse 
      effects/*pharmacokinetics
MH  - Injections, Intravenous
MH  - Injections, Subcutaneous
MH  - Middle Aged
MH  - Placebos
MH  - Recombinant Proteins/administration & dosage/adverse effects/pharmacokinetics
MH  - Single-Blind Method
MH  - Young Adult
EDAT- 2009/12/02 06:00
MHDA- 2010/05/01 06:00
CRDT- 2009/12/02 06:00
PHST- 2009/12/02 06:00 [entrez]
PHST- 2009/12/02 06:00 [pubmed]
PHST- 2010/05/01 06:00 [medline]
AID - 10.1185/03007990903432900 [doi]
PST - ppublish
SO  - Curr Med Res Opin. 2010 Feb;26(2):279-88. doi: 10.1185/03007990903432900.