Monograph: |
Methyl hydroxy benzoate
The properties are similar to propyl hydroxy benzoate, so see below at propyl hydroxy benzoate record for the details.
PROPYL HYDROXY BENZOATE
Adverse Effects and Precautions
Hypersensitivity reactions occur with the hydroxy-
benzoates. Generally these are of the delayed type,
appearing as contact dermatitis. Immediate reac-
tions with urticaria and bronchospasm have oc-
curred rarely.
Hypersensitivity. Immediate hypersensitivity reactions
have been reported following the injection of preparations
containing hydroxybenzoates. Delayed contact dermatitis
occurs more frequently, usually after topical application but
has also occurred after oral administration of an ester or of p-
hydroxybenzoic acid. The North American Contact Der-
matitis Group provided an incidence of 3%, while another
review7 of a large number of patients gave an incidence of
2.2%. However, subjects with healthy skin exposed to hy-
droxybenzoates, for example in cosmetics, are considered to
have a much lower incidence of reactions. Unusually, pa-
tients who have reacted to a hydroxybenzoate with a contact
dermatitis appear to be able to apply that preservative to an-
other unaffected site and yet not suffer a reaction: this has
been termed the paraben paradox.
Hypersensitivity reactions have occurred in patients given lo-
cal anaesthetics containing hydroxybenzoates and cross-
sensitivity between the two groups of drugs has been pro-
posed.
Neonates. An in-vitro study on serum from neonates with
hyperbilinibinaemia indicated that methyl hydroxybenzoate
at a concentration of 200 ng per mL of serum increased the
concentration of free unconjugated bilirubin and interfered
with the binding of bilirubin to serum proteins. Methyl hy-
droxybenzoate was present in an injection of gentamicin sul-
phate at a concentration of 1.3 to 1.8 mg per mL. Neither
gentamicin nor propyl hydroxybenzoate had a significant ef-
fect on bilirubin.'
Pharmacokinetics
Neonates. Methyl hydroxybenzoate present in an injectable
preparation of gentamicin was excreted in the urine of pre-
tenn infants following intramuscular injection to a variable
extent and mainly in the conjugated form, p-Hydroxybenzo-
ic acid was detected as a metabolite. The injection contained
3.6 mg of methyl hydroxybenzoate, 400 mg of propyl hy-
droxybenzoate, and 80 mg of gentamicin. Propyl hydroxy-
benzoate was also detected in the urine samples.
Uses
The hydroxybenzoate preservatives (parabens) are
alkyl esters of p-hydroxybenzoic acid with antibac-
terial and antifungal properties. They are active over
a broad pH range (4 to 8), though are generally more
active in acidic solutions. Activity increases with in-
creasing alkyl chain length but aqueous solubility
decreases, although this may be overcome by em-
ploying the more soluble sodium salts as long as the
pH of the preparation is not increased. Activity may
also be increased by combining two hydroxyben-
zoates with short alkyl chains. Another way of in-
creasing activity is to use a hydroxybenzoate with
propylene glycol.
Hydroxybenzoates are used as preservatives in phar-
maceutical preparations in concentrations of up to
0.25%. Methyl hydroxybenzoate and propyl hy-
droxybenzoate are used together in some prepara-
tions. There have been reports of the
hydroxybenzoates not being satisfactory preserva-
tives for ophthalmic preparations because of theil
relative lack of efficacy against some Gram-negative
bacteria, particularly Pseudomonas aeruginosa. The
hydroxybenzoate preservatives are widely used in
cosmetics and are also used for food preservation.
Hydroxybenzoates are also used for treating skin in-
fections.
|