PMID- 9253807
OWN - NLM
STAT- MEDLINE
DCOM- 19970923
LR  - 20190727
IS  - 0049-3848 (Print)
IS  - 0049-3848 (Linking)
VI  - 87
IP  - 1
DP  - 1997 Jul 1
TI  - High and constant plasma levels of tissue plasminogen activator and PEG-hirudin 
      can be achieved by subcutaneous delivery.
PG  - 123-9
AB  - Intramural thrombosis is a consistent finding in the arteries of patients who die 
      following coronary angioplasty. This thrombosis is thought to have a role in 
      restenosis, which is a common complication of coronary angioplasty. It has been 
      hypothesised that antithrombotics such as hirudin or tissue-type plasminogen 
      activator (tPA), may be therapeutically useful following angioplasty. This report 
      describes the bioavailability of both agents following subcutaneous (sc) 
      injection in cholesterol-fed rabbits. Intravenously delivered tPA has a half-life 
      of 3-5 minutes. The half-life of intravenously administered hirudin is less than 
      one hour in many species. In order to prolong the duration of action recombinant 
      hirudin was conjugated to polyethylene glycol (PEG). Polyethylene glycol 
      conjugated recombinant hirudin (PEG-rH) (0.7 mg/kg) antigen and activity were 
      measurable after just 1 hr, reaching a maximum (663 and 884 ng/ml respectively) 
      at 12 hours. Significant levels were present in rabbit plasma 24 hours after 
      injection. Subcutaneously delivered recombinant (r-tPA) (1 mg/kg) was present in 
      significant amounts 1 hr after injection, reaching a maximum (92 IU/ml) at 2 
      hours. Levels of tPA at 9 hours were approximately 80x normal circulating levels. 
      High and constant levels of functional activity of both PEG-rH and r-tPA in 
      rabbit plasma are achieved by subcutaneous delivery.
FAU - Humphries, J
AU  - Humphries J
AD  - Department of Surgery, St Thomas' Hospital, London, UK.
FAU - Lattimer, C
AU  - Lattimer C
FAU - Smith, A
AU  - Smith A
FAU - McGuinness, C L
AU  - McGuinness CL
FAU - Whitton, C
AU  - Whitton C
FAU - Gaffney, P J
AU  - Gaffney PJ
FAU - Burnand, K G
AU  - Burnand KG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 0 (Antithrombins)
RN  - 0 (Hirudins)
RN  - 0 (polyethyleneglycol-hirudin)
RN  - EC 3.4.21.- (Plasminogen Activators)
RN  - EC 3.4.21.68 (Tissue Plasminogen Activator)
SB  - IM
MH  - Animals
MH  - Antithrombins/*administration & dosage/pharmacokinetics
MH  - Diet, Atherogenic
MH  - Hirudins/administration & dosage/*analogs & derivatives/blood/pharmacokinetics
MH  - Injections, Subcutaneous
MH  - Plasminogen Activators/*administration & dosage/pharmacokinetics
MH  - Rabbits
MH  - Thrombosis/blood/*drug therapy
MH  - Tissue Plasminogen Activator/*administration & dosage/blood/pharmacokinetics
EDAT- 1997/07/01 00:00
MHDA- 1997/07/01 00:01
CRDT- 1997/07/01 00:00
PHST- 1997/07/01 00:00 [pubmed]
PHST- 1997/07/01 00:01 [medline]
PHST- 1997/07/01 00:00 [entrez]
AID - S0049-3848(97)00111-4 [pii]
AID - 10.1016/s0049-3848(97)00111-4 [doi]
PST - ppublish
SO  - Thromb Res. 1997 Jul 1;87(1):123-9. doi: 10.1016/s0049-3848(97)00111-4.