Pharmacokinetics of enrofloxacin and ciprofloxacin in Atlantic horseshoe crabs (Limulus polyphemus) after single injection

Abstract

The pharmacokinetics of enrofloxacin and the metabolite ciprofloxacin were studied in horseshoe crabs after a single injection of 5 mg/kg. Twelve Atlantic horseshoe crabs (Limulus polyphemus) of undetermined age were injected with enrofloxacin into the dorsal cardiac sinus. Hemolymph samples were collected by syringe and needle at regular intervals for 120 hr. Samples were analyzed by high-pressure liquid chromatography and compartmental analysis performed on the results. Following injection, the elimination half-life (T½), peak concentration, area under the curve (AUC), and volume of distribution (VD) for enrofloxacin were 27.9 (29.13) hr, 8.98 (18.09) μg/ml, 367.38 (35.41) hr μg/ml, and 0.575 (20.48) L/kg, respectively (mean value, CV%). For ciprofloxacin, the elimination T½, peak concentration, and AUC were 61.36 (34.55) hr, 2.34 (24.11) μg/ml, and 304.46 (24.69) μg hr/ml. In these animals, the ciprofloxacin concentrations comprised an average of 45.8% of the total fluoroquinolone concentrations, which is substantial compared to other marine invertebrates. The total AUC produced (sum of enrofloxacin and ciprofloxacin) was 682.69 ± 180.61 μg hr/ml. Concentrations that were achieved after a single dose of 5 mg/kg horseshoe crabs were sufficient to treat bacteria susceptible to enrofloxacin and ciprofloxacin.

Transcriptomics Analysis of the Toxicological Impact of Enrofloxacin in an Aquatic Environment on the Chinese Mitten Crab (Eriocheir sinensis)

“…Although enrofloxacin is approved for aquaculture in China [8], when used in large quantities, the antimicrobial remains in the aquaculture water and sediment accumulates in aquatic animals. Pharmacokinetic 2 of 14 studies on enrofloxacin in crustaceans, including the Eriocheir sinensis [9][10][11], Atlantic horseshoe crab [12], and giant mud crab [13], have been reported. Enrofloxacin can be biotransformed in vivo into its major metabolite, ciprofloxacin, in crabs.…”

Enrofloxacin Pharmacokinetics and Sampling Techniques in California Sea Hares (Aplysia californica)

“…In addition, although the average peak concentration and AUC of enrofloxacin in horseshoe crabs (9.0 µg/mL and 367.4 h×µg/ mL, respectively) were higher than those of Aplysia (3.0 µg/mL and 41.6 h×µg/mL, respectively), they were closer than those for sea urchins. 9,19 Expanding the comparison to include many species of fish, 4,5,13,14,17 the elimination half-life and volume of distribution of enrofloxacin in Aplysia are consistent with those of other invertebrate and marine vertebrate species.…”

“…Pharmacokinetic parameters (Table 1) were consistent with data in some invertebrate species but not others. 7,9,19,20 Enrofloxacin pharmacokinetic studies have been performed in cuttlefish, sea stars, mud crab, horseshoe crabs, and sea urchins. 5,7,9,19,20 Data from a pharmacokinetic analysis of cuttlefish (a mollusk species like Aplysia, but from a different taxonomic class and a species with a closed rather than open circulatory system)…”

Enrofloxacin—The Ruthless Killer of Eukaryotic Cells or the Last Hope in the Fight against Bacterial Infections?

“…The elimination of enrofloxacin varies widely among species. For comparison, the elimination half-life (t 1/2 ) after intravenous administration was as follows: in cows, 1.5 h [ 41 ], dogs, 2 h [ 42 ], sheep, 4.31 h [ 43 ], cats, 5.6 h [ 44 ], pigs, 9.64 h [ 45 ], horses, 9.9 h [ 46 ], broilers, 12.84 h [ 47 ], African penguins, 13.67 h [ 48 ], American alligators, 21.05 h [ 21 ], and Atlantic horseshoe crabs, 27.9 h [ 49 ].…”