HI‐6 and 2‐pam in sheep: Pharmacokinetics and effects on muscle tissue following intramuscular injection

Moore, David H.; Hayward, Isaac J.; F, Tucker; Lukey, Brian J.

doi:10.1002/bdd.2510120307

Cited by 9 publications

(4 citation statements)

References 15 publications

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“…Blood samples (0.4mL) from the carotid artery were drawn 5, 4, and 3min before injection and 0, 1, 2, 5, 10,15,20,25,30,40,50, 60, 90, 120, 150, 180, 210,240,270,300,330, and 360min postinjection. Part of each sample (0-3 mL) collected in heparinized syringes was used for measurements of Pao2, Pacoz, and pH by an ABL 2 MT analyser (Radiometer A7S).…”

Section: Determination Of Acetylcholinesterase Activitymentioning

confidence: 99%

Pharmcokinetics of HI‐6 and atropine in anaesthetized pigs after administration by a new autoinjector

Nyberg

Cassel

Jeneskog

et al. 1995

Biopharm & Drug Disp

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A newly developed autoinjector (Astra Tech, Sweden) containing 500 mg HI-6 and 2 mg atropine sulphate was tested in anaesthetized normal pigs. The pharmacokinetics and pharmacodynamics of the drugs after administration by the autoinjector were compared with those after conventional needle and syringe delivery intramuscularly and intravenously. Cardiopulmonary parameters were monitored and serum concentrations of oxime, atropine, and acetylcholinesterase were determined in blood samples taken at intervals over a 6 h period postinjection. After injection in anaesthetized pigs, both HI-6 and atropine were absorbed rapidly and completely from the injection site. Therapeutic serum concentrations of HI-6, arbitrarily taken as 4 micrograms mL-1, were reached within 1 min of intravenous and autoinjector administration, and within 5 min of intramuscular injection. The concentrations remained above this level for 3-4 h. There were no significant changes in acetylcholinesterase activity, mean arterial blood pressure, or respiration frequency after injection of HI-6 and atropine sulphate. The heart rates increased significantly after administration of the two drugs (cardioacceleration defined as > or = 5% increase in heart rate), regardless of the technique employed. Our results show that HI-6 and atropine sulphate can be given intramuscularly by the new autoinjector with the same effectiveness and speed as when given intravenously. Irrespective of the injection technique, no overt signs of toxicity were observed at the drug concentrations used.

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Section: Determination Of Acetylcholinesterase Activitymentioning

confidence: 99%

Pharmcokinetics of HI‐6 and atropine in anaesthetized pigs after administration by a new autoinjector

Nyberg

Cassel

Jeneskog

et al. 1995

Biopharm & Drug Disp

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“…It has been shown that therapeutic concentrations of 2-PAM are quite high in rat plasma and serum (1.4-5.5 mg/ml; [27] up to 100 mg/ml; [26] 0.7-3.3 mg/ml [28] ), in sheep plasma (up to 7 mg/ ml, [33] and in human plasma and serum (0.5-3 mg/ml; [23,24] 3-6 mg/ml; [25] 3-15 mg/ml [12,13] ). Concentrations in human urine were more than 100-times higher (250-2000 mg/ml [20] ).…”

Section: Resultsmentioning

confidence: 99%

Quantification of pralidoxime (2‐PAM) in urine by ion pair chromatography‐diode array detection: application to in vivo samples from minipig

John

Eddleston

Clutton

et al. 2011

Drug Testing and Analysis

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Pralidoxime (2-PAM) is a monopyridinium oxime used as an antidote for the treatment of poisoning with organophosphorus (OP) compounds, for example, pesticides and nerve agents, reactivating OP-inhibited acetylcholinesterase. However, appropriate dosing and efficacy remains a matter of discussion requiring experimental data. Therefore, we developed and validated an ion pair chromatography-diode array detection (IPC-DAD) method suitable for quantitative analysis of 2-PAM in human and porcine urine. Before injection of 20 µl, urine was acidified with trichloroacetic acid, mixed with internal standard (pyridine-4-aldoxime, 4-PAO), and diluted with IPC solvent yielding a total dilution of 1:49.5 and a 100% recovery. Isocratic separation was carried out at 25 °C on a LiChrospher 60 RP-select B column (125 x 4.0 mm I.D.) using phosphate buffer (7.5 mM Na(2) HPO(4) , 7.5 mM KH(2) PO(4) , pH 2.6) mixed with octanesulfonate (2.5 mM) as ion pair reagent and acetonitrile (6% v/v) as organic modifier (1 ml/min). 2-PAM was detected at 293 nm and 4-PAO at 275 nm. The method is rugged, selective, and characterized by good intra-day and inter-day precision (RSD, 1.3-6.0%) and accuracy (88-100%) with a limit of detection at 4.9 µg/ml, a limit of quantification at 9.8 µg/ml, and a broad calibration range from 4.9-2500 µg/ml. The procedure was applied to urine samples obtained from dimethoate poisoned minipigs receiving 2-PAM therapy (intravenous bolus injection and infusion). Results indicate that 60-80% of infused 2-PAM is rapidly (within 1-2 h) excreted in the urine.

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“…170–206 min). Parameters are species‐dependent as shown for example, for man, rat, and sheep . Elimination of 2‐PAM is best described by a two‐compartment open model not showing significant binding to plasma proteins …”

Section: Introductionmentioning

confidence: 99%

“…As summarized in Table , diverse IPC modifications were introduced in the following years varying the stationary phase material and mobile phase composition. IPC was applied to qualitative and quantitative analysis of neat solutions, pharmaceutical formulations and biological specimen from different species including plasma and serum, urine, and brain tissue (Table ).…”

Section: Introductionmentioning

confidence: 99%

Review of UV spectroscopic, chromatographic, and electrophoretic methods for the cholinesterase reactivating antidote pralidoxime (2‐PAM)

John¹,

Blum

2011

Drug Testing and Analysis

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Pralidoxime (2-PAM) belongs to the class of monopyridinium oximes with reactivating potency on cholinesterases inhibited by phosphylating organophosphorus compounds (OPC), for example, pesticides and nerve agents. 2-PAM represents an established antidote for the therapy of anticholinesterase poisoning since the late 1950s. Quite high therapeutic concentrations in human plasma (about 13 µg/ml) lead to concentrations in urine being about 100 times higher allowing the use of less sensitive analytical techniques that were used especially in the early years after 2-PAM was introduced. In this time (mid-1950s until the end of the 1970s) 2-PAM was most often analyzed by either paper chromatography or simple UV spectroscopic techniques omitting any sample separation step. These methods were displaced completely after the establishment of column liquid chromatography in the early 1980s. Since then, diverse techniques including cation exchange, size-exclusion, reversed-phase, and ligand-exchange chromatography have been introduced. Today, the most popular method for 2-PAM quantification is ion pair chromatography often combined with UV detection representing more than 50% of all column chromatographic procedures published. Furthermore, electrophoretic approaches by paper and capillary zone electrophoresis have been successfully used but are seldom applied. This review provides a commentary and exhaustive summary of analytical techniques applied to detect 2-PAM in pharmaceutical formulations and biological samples to characterize stability and pharmacokinetics as well as decomposition and biotransformation products. Separation techniques as well as diverse detectors are discussed in appropriate detail allowing comparison of individual preferences and limitations. In addition, novel data on mass spectrometric fragmentation of 2-PAM are provided.

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HI‐6 and 2‐pam in sheep: Pharmacokinetics and effects on muscle tissue following intramuscular injection

Cited by 9 publications

References 15 publications

Pharmcokinetics of HI‐6 and atropine in anaesthetized pigs after administration by a new autoinjector

Pharmcokinetics of HI‐6 and atropine in anaesthetized pigs after administration by a new autoinjector

Quantification of pralidoxime (2‐PAM) in urine by ion pair chromatography‐diode array detection: application to in vivo samples from minipig

Review of UV spectroscopic, chromatographic, and electrophoretic methods for the cholinesterase reactivating antidote pralidoxime (2‐PAM)

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