A non‐invasive and quantitative method for the study of tissue injury caused by intramuscular injection of drugs in horses

Toutain, Pierre‐Louis; Lassourd, V.; Costes, G.; Alvinerie, M.; Bret, L.; Lefebvre, Henri; Braun, Jean‐Pierre

doi:10.1111/j.1365-2885.1995.tb00583.x

Cited by 37 publications

(18 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…injections of irritating drugs [24,25]. Becker et al [3] reported that sulphadoxine-trimethoprim caused a marked increase of CK after s.c. administration: the increase was about 20% of that caused by i.m.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of sulphadoxine and trimethoprim and tissue irritation caused by two sulphadoxine-trimethoprim containing products after subcutaneous administration in pre-ruminant calves

Kaartinen

Gips²,

Laurila

et al. 2000

Vet. Res.

View full text Add to dashboard Cite

-The pharmacokinetics of sulphadoxine-trimethoprim was studied in 6 pre-ruminant calves using two different products. Product A, which contained 200 mg sulphadoxine and 40 mg trimethoprim per mL, was administered intravenously or subcutaneously at a dosage of 25 mg sulphadoxine and 5 mg trimethoprim·kg -1 bodyweight. Product B, containing 62.5 mg sulphadoxine and 12.5 mg trimethoprim per mL plus lidocaine (1 mg·mL -1 ), was given subcutaneously at the same dosage. After intravenous administration of product A the mean time of half-life of elimination phase (t 1/2 ) for sulphadoxine was 12.9 h, steady-state volume of distribution (V d(ss) ) was 0.44 L·kg -1 and clearance was 0.024 L·kg -1 ·h -1 . Respective values for trimethoprim were 1.9 h, 2.0 L·kg -1 and 0.9 L·kg -1 ·h -1 . After subcutaneous administration, the bioavailability of sulphadoxine was 96% and 98% and the time to reach a maximum concentration was 6.3 and 8.0 h for products A and B, respectively. The C max for trimethoprim was higher for product A (0.49 µg·mL -1 ) than for product B (0.32 µg·mL -1 ) (p = 0.014). Slow absorption from the injection site appeared to delay the elimination of trimethoprim after subcutaneous administration when compared to that after intravenous administration: apparent elimination t 1/2 for trimethoprim after intravenous administration of product A was 1.9 h compared to 3.9 h and 3.6 h after subcutaneous administration of products A and B, respectively. The difference between intravenous and subcutaneous administrations was statistically significant (p < 0.05). Also the mean residence time was significantly shorter (p < 0.05) after intravenous administration (2.4 h) than that after subcutaneous administration of product A (6.9 h) and B (7.1 h). The bioavailability of trimethoprim was lower than that of sulphadoxine: 76% and 74% for products A and Vet. Res. 31 (2000)

show abstract

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of sulphadoxine and trimethoprim and tissue irritation caused by two sulphadoxine-trimethoprim containing products after subcutaneous administration in pre-ruminant calves

Kaartinen

Gips²,

Laurila

et al. 2000

Vet. Res.

View full text Add to dashboard Cite

show abstract

“…and im. administration and a plasma terminal half-life of 112 ± 18 min and 11.8 ± 5.3 h, respectively [122]. …”

Section: Drug Examplesmentioning

confidence: 99%

Flip-flop Pharmacokinetics – Delivering a Reversal of Disposition: Challenges and Opportunities During Drug Development

Yáñez

Remsberg

Sayre

et al. 2011

Therapeutic Delivery

201

108

View full text Add to dashboard Cite

Flip-flop pharmacokinetics is a phenomenon often encountered with extravascularly administered drugs. Occurrence of flip-flop spans preclinical to human studies. The purpose of this article is to analyze both the pharmacokinetic interpretation errors and opportunities underlying the presence of flip-flop pharmacokinetics during drug development. Flip-flop occurs when the rate of absorption is slower than the rate of elimination. If it is not recognized, it can create difficulties in the acquisition and interpretation of pharmacokinetic parameters. When flip-flop is expected or discovered, a longer duration of sampling may be necessary in order to avoid overestimation of fraction of dose absorbed. Common culprits of flip-flop disposition are modified dosage formulations; however, formulation characteristics such as the drug chemical entities themselves or the incorporated excipients can also cause the phenomenon. Yet another contributing factor is the physiological makeup of the extravascular site of administration. In this article, these causes of flip-flop pharmacokinetics are discussed with incorporation of relevant examples and the implications for drug development outlined.

show abstract

“…Creatine kinase has been shown to be reliable indicator of tissue damage (Steiness et al 1978;Toutain et al 1995). injection were monitored clinically and by determination of serum creatine kinase (CK) activity.…”

Section: Analysis Of Tissue Irritationmentioning

confidence: 99%

Pharmacokinetics of enrofloxacin in horses after single intravenous and intramuscular administration

Kaartinen

Panu

Pyörälä

1997

Equine Veterinary Journal

View full text Add to dashboard Cite

Summary Pharmacokinetic behaviour of enrofloxacin was studied in 6 horses after intravenous (i.v.) or intramuscular (i.m.) administration of enrofloxacin (5 mg/kg bwt). Concentrations of enrofloxacin and ciprofloxacin were measured by high performance liquid chromatography in serum. Antimicrobial activity of the samples was determined with an agar‐diffusion technique. Reactions at the site of i.m. injection were monitored clinically and by determination of serum creatine kinase (CK) activity. After i.v. administration, elimination half‐life of enrofloxacin was 4.4 h and volume of distribution was 2.3 1/kg bwt. Enrofloxacin was rapidly metabolised to ciprofloxacin. The half‐life of ciprofloxacin parallelled that of the parent drug, its concentration in serum reached 20–35% of that of the parent drug. After i.m. administration, elimination half‐life of enrofloxacin was longer (9.9 h) than after i.v. administration. Mean absorption time of enrofloxacin was also long (9.9 h). No statistically significant differences were found when half‐life and mean residence time of antimicrobial activity were compared with those of enrofloxacin and ciprofloxacin from chemically analysed data. Intramuscular injection of enrofloxacin was found to be very irritating. After i.m. administration, CK activity in serum, compared with pre‐injection levels, increased over 10‐fold. CK activity also stayed high during the 32 h follow‐up period. Clinical reactions, such as swelling or tenderness at the i.m. injection sites, were observed in 2 horses.

show abstract

A non‐invasive and quantitative method for the study of tissue injury caused by intramuscular injection of drugs in horses

Cited by 37 publications

References 22 publications

Pharmacokinetics of sulphadoxine and trimethoprim and tissue irritation caused by two sulphadoxine-trimethoprim containing products after subcutaneous administration in pre-ruminant calves

Pharmacokinetics of sulphadoxine and trimethoprim and tissue irritation caused by two sulphadoxine-trimethoprim containing products after subcutaneous administration in pre-ruminant calves

Flip-flop Pharmacokinetics – Delivering a Reversal of Disposition: Challenges and Opportunities During Drug Development

Pharmacokinetics of enrofloxacin in horses after single intravenous and intramuscular administration

Contact Info

Product

Resources

About