Cardiovascular effects and fatalities associated with intravenous administration of doxycycline to horses and ponies

Riond, J.‐L.; Riviere, Jim E.; Duckett, Wendy M.; Atkins, Clarke E.; Jernigan, A.D; Rikihisa, Yasuko; Spurlock, S. L.

doi:10.1111/j.2042-3306.1992.tb02777.x

Cited by 52 publications

(35 citation statements)

References 17 publications

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“…If a much longer apparent elimination half-life following extravascular dosing is observed compared with the IV route, it suggests that flip-flop pharmacokinetics is occurring [24]. However this is not possible with Dox considering that IV administration of this drug in horses is not recommended [9,10]. Thus, applying the following equation and based on information taken from published work [25,26], a flip-flop condition may be demonstrated with the following equation:…”

Section: Discussionmentioning

confidence: 99%

“…More recently, however, Chavda et al [30] include Dox in Class I; that is, Dox is highly soluble and highly permeable, which shows no coherence when analyzing its reported absolute bioavailability in horses i.e., from 2.8% to 17% [12,31]. In this study, absolute bioavailability of Dox for the two long-action formulations (Dox-pol and Dox-β) was not determined because the IV kinetics of the drug is needed, and risk of cardiovascular toxicity was avoided [10]. The F rel for Dox-pol and Dox-β was 548% and 48%, respectively, as compared to Dox-a, in non-fasted horses.…”

Section: Discussionmentioning

confidence: 99%

“…The intravenous use should also be avoided, as it can cause supraventricular tachycardia, systemic arterial hypertension, clinical signs of discomfort, cardiovascular collapse and even death in horses [9,10]. …”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of a peroral single dose of two long-acting formulations and an aqueous formulation of doxycycline hyclate in horses

et al. 2013

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BackgroundDoxycyline (Dox) is a semisynthetic antibacterial drug with pharmacological advantages over its parent drug (tetracycline) in the treatment of various bacterial diseases in horses. Yet, at present a horse-customized pharmaceutical formulation is not available. Based on its pharmacokinetic/pharmacodynamic (PK/PD) ratio, Dox is considered a time-dependent antibacterial drug and ideally expected to achieve sustained plasma drug concentrations both at or slightly above the minimal inhibitory concentration (MIC) level for as long as possible between dosing intervals. Hence, the objective of this study was to formulate two long-acting (LA) doxycyline hyclate (Dox-h) formulations for oral administration and define their pharmacokinetics in non-fasted adult horses to obtain better bioavailability and longer mean residence time, features needed to comply better with its pharmacokinetic/pharmacodynamic (PK/PD) ratios.ResultsPharmacokinetic parameters were determined after the oral administration of a single 10 mg/kg bolus dose of two 20% Dox-h formulations: one based on a β cyclodextrin (Dox-β) matrix and a second one on a poloxamer (Dox-pol) matrix. The results were compared with the pharmacokinetics of a single 10 mg/kg bolus oral dose of a freshly made aqueous Dox-h solution (Dox-a). Dox-pol showed the greatest values for relative bioavailability (548%); maximum serum concentration (Cmax) value was 1.3 ± 0.7 μg/mL with time to reach the Cmax (Tmax) of 5.9 ± 1.7 h, area under the curve (AUC) of 17.0 ± 2.2 μg h/ml and elimination half-life (T½ β) of 4.9 ± 1.0 h.ConclusionsConsidering a minimal inhibitory concentration MIC of 0.25 μg/mL, clinically effective plasma concentrations might be obtained for up to 24 h administering Dox-pol. This is an oral paste formulation that might optimize the use of Dox-h in horses in terms of PK/PD ratio congruency, and it is likely that it may also improve prescription compliance due to its ease of administration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics of a peroral single dose of two long-acting formulations and an aqueous formulation of doxycycline hyclate in horses

et al. 2013

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“…Supraventricular tachycardia has been reported only on horses after i.v. infusion of doxycycline [4]. Atrial dysrhythmias were described as complications of intrapericardial doxycycline sclerosis in the treatment of malignant pericardial effusion [5].…”

Section: Discussionmentioning

confidence: 99%

Chronic intoxication by doxycycline use for more than 12 years

Westermann

Böhm

Bonsmann

et al. 1999

Journal of Internal Medicine

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Abstract. Westermann GW, Bo Èhm M, Bonsmann G, Rahn KH, Kisters K (Westfa Èlische WilhelmsUniversity, Mu È nster, Germany). Chronic intoxication by doxycycline use for more than 12 years (Case Report). J Intern Med 1999; 246: 591±592.We report the clinical case of a 12-years' intoxication by doxycycline. A patient with a depersonalization and derealization syndrome took 1 g doxycycline per day. In addition to hepatocellular necrosis with cholestasis, nephrotoxicity, leukopenia, anaemia and skin hyperpigmentation he suffered from hitherto unreported adverse cardiac events as intermittent supraventricular tachycardia and sporadic Wenckebach heart block. Despite a long period of self-medication these side-effects were reversible.

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“…Er wird nach i.v. Verabreichung von Thimethoprim (Alexander und Collett 1975), potenzierten Sulfonamiden (Eikmeier 1986, Dick und White 1987, Thylor et al 1988, Gray et al 1990), Doxycycline (Riond et al 1992 AM 1 =TMP/S-Präparate AM 5 =,,Stoffwechsel-Präparate" AM 2 = andereAntibiotika AM 6 =,,Kolik-Präparate" AM 3 = Vitaminpräparate AM 7 = Sedativa und Narkotika AM 4 =Antiphlogistika AM B =,,Gynäkologische Präparate" AM 9 = "Lungentherapeutika" AM 1 =TMP/S-Präparate AM 5 =,,Stoffwechsel-Präparate" AM 2 = andere Antibiotika AM 6 =,,Kolik-Präparate" AM 3 = Vitaminpräparate AM 7 = Sedativa und Narkotika AM 4 = Antiphlogistika AM B =,,Gynäkologische Präparate" AM I = ,,Lungentherapeutika" In den Abbildungen 5a und 5b ist die Injektionsgeschwindigkeit in Bezug zu den unerwünschten Arzneimittelwirku.tg.n dargestellt. Daraus ist ersichtlich, daß die relative Häufigkeit der langsamen, schnelleren und schnellen i.v.…”

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