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Does anyone have any experience with formulations for iv use that are
at a high pH (pH 9 - ca 75 ml / adult with a low
buffering capacity)? I am worried about venous irritation.
Many thanks
Gordon Rigg
University of Manchester.
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[A few replies - db]
Date: Sat, 5 Feb 2000 00:13:02 -0700 (MST)
X-Sender: ml11439.-a-.pop.goodnet.com
To: PharmPK.at.boomer.org
From: ml11439.aaa.goodnet.com (Michael J. Leibold)
Subject: Re: PharmPK Venous Irritation and High pH
Gordon,
Parenteral phenytoin is adjusted to pH 12 with sodium hydroxide to
maintain it solubility in a 40% propylene glcol and 10% alcohol diluent.
The rate of administration should not exceed 50mg/min to avoid the
toxicity of the propylene glcyol component which can cause cardiovascular
collapse and CNS depression. The IM route is contraindicated due to
precipitaion of phenytoin acid crystals as the tissue buffers decrease
the pH and the propylene glycol is absorbed from the injection site.
Sometimes phenytoin is administered as IV infusion in saline, but not
in dextrose due to the acidic pH. If infused in saline, a 0.22 micron
in-line IV filter should be employed to remove phenytoin microcyrstals
formed as the propylene glycol/alcohol components are diluted, and the
pH decreases.
The phosphate ester prodrug, fosphenytoin, overcomes the solubility
problems of phenytoin allowing IM administration and IV infusion without
the need for an in-line .22 micron filter.
Regarding venous irritation:
Pain, inflammation, tissue necrosis and/or sloughing at the site
of injection may occur, and may result tissue damage severe enough to
result in amputation. As result, improper administration should be
avoided to prevent subcutaneous/perivascular administration, and IV
administration should be followed with saline flushes to avoid local
tissue irritation from the sodium hydroxide buffer.
Mike Leibold, PharmD, RPh
ML11439.-a-.goodnet.com
---
From: q.-at-.gcpl.co.uk
To: PharmPK.-a-.boomer.org
Date: Sat, 5 Feb 2000 11:22:13 -0000
Subject: Re: PharmPK Venous Irritation and High pH
Reply-to: q.aaa.gcpl.co.uk
Priority: normal
Dear Gordon:
Thiopenton is a classic example of a high pH (circa 11) fluid for IV
injection and there is a literature on the subject because it was the
standard anaesthetic induction drug for so many years. The risk
was that if anaesthetists used the medial vein in the antecubital
fossa for induction and there was extravasation, then the ulnar
artery or nerve could become embroiled in the inflammation with
dire consequences. Another is IV diazepam. The peculiarity of that
drug was that the inflammation, manifest as swelling, pain and
hardness of the venous track in the arm, would appear only after
several days, often over a week after the injection.
Andrew Sutton
Guildford Clinical Pharmacology
---
From: "bmurray"
To:
Subject: Re: PharmPK Venous Irritation and High pH
Date: Sat, 5 Feb 2000 13:18:21 -0800
X-Priority: 3
Check out Gancicylovir (it has characteristics similar to what you're
talking about).
Bill Murray Pharm.D.
Children's Hospital San Diego
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)