@article{3151353,
    title = "The Influence of Diphenhydramine Administration on Lidocaine Protein
Binding in Rat Serum and Tissues",
    author = "Tigka, E. and Alevizou, A. and Kotsiou, A. and Tesseromatis, C.",
    journal = "International Journal of Pharmacology",
    year = "2011",
    volume = "7",
    number = "8",
    pages = "880-883",
    publisher = "Asian Network for Scientific Information (ANSINET)",
    issn = "1811-7775, 1812-5700",
    doi = "10.3923/ijp.2011.880.883",
    keywords = "Antihistamine; local anaesthetic; alpha-1-acid glycoprotein;
displacement; pharmacokinetics interaction",
    abstract = "Lidocaine is an amide type local anaesthetic and diphenhydramine is a
first-generation antihistamine drug. The aim of the present study was to
investigate the influence of diphenhydramine co-administration on the
extent of lidocaine binding to rat serum and maxillofacial tissue
proteins in order to determine a possible synergistic action that could
enhance lidocaine’s anaesthetic/analgesic activity. Twenty-eight Wistar
rats divided in 4 groups (I, II, Ill, IV) received lidocaine in the
masseter muscle. Groups II and IV received diphenhydramine per os 2 h
before lidocaine administration. Groups I and II were sacrificed after
15 min and groups III and IV 30 min after lidocaine injection. Masseter
and mandible samples were isolated and incubated in NaCl 0.9% solution
while serum was obtained through blood centrifugation. Free lidocaine
fraction in the tissues’ incubation medium and the serum was obtained
through ultrafiltration and determined by radioscopic method in a
beta-counter Lidocaine’s free fraction levels (mu g g(-1)) were enhanced
after 15 min under diphenhydramine co-administration in all samples from
(7.1319 +/- 1.4066) x 10(-4) to (12.1097 +/- 3.7528) x 10(-4) in serum,
from 0.9339 +/- 0.3077 to 2.6791 +/- 1.1648 in masseter (p<0.01) and
from 0.3898 +/- 0.0879 to 0.6918 +/- 0.2743 in mandible (p<0.05). A
statistically significant increase in free anaesthetic levels was also
noticed after 30 min in serum from (8.6227 +/- 0.6902) x 10(-4) to
(13.9518 +/- 4.9849) x 10(-4) (p<0.05). Lidocaine’s increase could
probably be attributed to mechanisms influencing its protein binding
properties. Consequently, a possible synergistic action of the two
drugs’ combination is demonstrated which could enhance lidocaine’s
anaesthetic action, affecting depth and duration of anaesthesia."
}