Ocular penetration of cephalexin in the rabbit.

Abstract

The cephalosporin group of antibiotics has gained widespread use in combating resistant infections. Because of the necessity for intravenous administration of cephalothin, and the intramuscular route for cephaloridine, the development of a new member of this series which is effective orally prompted study of its penetration into the eye. This is the first reported study of the passage of cephalexin into the aqueous humour. Material and methodsCephalexin was provided in pure powdered form by the manufacturer through the courtesy of Dr. L. D. Bechtold. Preliminary experiments performed in the Medical Research Laboratory of the Eli Lilly Company had shown that in man nearly I 00 per cent. of orally administered cephalexin is absorbed from the gastrointestinal tract within 6o to go minutes, and that 98 per cent. is excreted unconjugated in the urine after 6 hours. For the present study, doses of I25 mg. powdered cephalexin were dissolved in sterile distilled water and administered by gastric lavage to rabbits. Healthy adult rabbits were weighed, and only animals of the same weight range selected, so that the same dosage was given to all animals-50 mg./kg. as a single oral dose. Samples of blood and aqueous humour were then collected at intervals of from i to 8 hours, and were frozen within 20 minutes after being obtained. Non-toxic pink-topped Vacutainer tubes (NT3206) were used for collection and freezing of the blood samples. After topical o05 per cent. proparacaine hydrochloride anaesthesia, disposable sterile tuberculin syringes with No. 27 gauge needles were used for anterior chamber paracentesis. Anterior chamber taps were performed only on white and quiet (i.e. non-inflamed) eyes. No paracentesis was repeated on an eye within 48 hours of a previous tap. The specimens were packed in dry ice and shipped via air express to the Lilly Medical Research Laboratories for bioassay. Control sera and aqueous humour samples obtained from normal animals were sent with each shipment. The specimens forwarded to the laboratory were identified by code number only, so that those performing the bioassay determinations had no information concerning time, dose, or which were controls. ResultsThis study consisted of seventy specimens (35 each of serum and matched aqueous humour) from rabbits after oral cephalexin, and eight specimens (4 each of serum and matched aqueous humour) from healthy control rabbits. A total of 78 specimens was thus studied-39 serum and 39 aqueous humour. The Sarcina lutea disc-plate technique of bioassay was employed at the Lilly Laboratory, and the results were reported in jig./ml. No activity was found in any of the eight control specimens. The other data are summarized in the (Table, overleaf) and shown graphically in (Fig. I, overleaf).

Pharmacokinetics and tissue fluid distribution of cephalexin in the horse after oral and i.v. administration

“…This is characteristic of a poorly lipophilic drug. Cephalexin has previously been shown to penetrate into the aqueous humor of noninflamed rabbit eyes at concentrations as high as 15-20% of plasma concentrations (Gager et al, 1969). However, the difference between the study in rabbits and in these horses is that the rabbits were administered a higher dose (50 mg/kg) and the aqueous levels peaked at 1 h after dosing, which was earlier than the sampling times of the horses in the present study.…”

“…This is characteristic of a poorly lipophilic drug. Cephalexin has previously been shown to penetrate into the aqueous humor of noninflamed rabbit eyes at concentrations as high as 15–20% of plasma concentrations (Gager et al. , 1969).…”

Partitioning of Cephalexin in Ionic Liquid Aqueous Two‐Phase System Composed of 1‐Butyl‐3‐Methylimidazolium Tetrafluoroborate and ZnSO4

“…e ionization states of CEX molecules vary with pH in the aqueous solution [26,27]. It is positively charged below its isoelectric point of 4.3 and negatively charged above pH 4.3 [15]. e pH of ZnSO 4 solutions is around 3.0.…”

“…Cephalexin (CEX, Figure 1) is hydrosoluble cephalosporins antibiotics. CEX is an amphoteric compound, and its isoelectric point was 4.3 [15]. e conventional methods currently used to extract CEX include liquid-liquid extraction [16], ultra�ltration [17], deproteination by organic solvent [18], solid-phase extraction [19,20], and liquid membrane extraction [21,22].…”

Distribution of liposome-incorporated carboxyfluorescein in rabbit eyes

“…Numerous pharmacological studies have reported only limited d r u g uptake b y the eye after local instillation (Barry a n d Rousseau 1969, Barza et al 1973, Furgiuele 1967, Gager et al 1969, Janes and Stiles 1963, Levine a n d Aronson 1970). D r u g s incorporated into liposomes, however, appear to penetrate better into the eye a n d to have higher local concentrations.…”