I.v. ketoprofen for analgesia after tonsillectomy: comparison of pre- and post-operative administration.

We have evaluated the safety and efficacy of ketoprofen during tonsillectomy in 106 adults receiving standardized anaesthesia. Forty-one patients received ketoprofen 0.5 mg kg(-1) at induction ('pre' ketoprofen group) and 40 patients after surgery ('post' ketoprofen group), in both cases followed by a continuous ketoprofen infusion of 3 mg kg(-1) over 24 h; 25 patients received normal saline (placebo group). Oxycodone was used for rescue analgesia. Patients in the ketoprofen groups experienced less pain than those in the placebo group. There was no difference between the study groups in the proportion of patients who were given oxycodone during the first 4 h after surgery. However, during the next 20 h, significantly more patients in the placebo group (96%) received oxycodone compared with patients in the 'pre' ketoprofen group (66%) and the 'post' ketoprofen group (55%) (P=0.002). Patients in the placebo group received significantly more oxycodone doses than patients in the two ketoprofen groups (P=0.001). Two patients (5%) in the 'pre' ketoprofen group and one (3%) in the 'post' ketoprofen group had post-operative bleeding between 4 and 14 h. All three patients required electrocautery.

Ion mobility spectrometric monitoring of phosdrin from foliage in greenhouse.

The monitoring of Phosdrin (mevinphos; insecticide) from foliage and foliage extracts was achieved by an aspiration-type ion mobility spectrometer. This technique is based on ion mobility, which is proportional to the molecular weight, shape, and charge. The operation principle of the ion mobility spectrometer is to measure mobility distribution changes of product and reactant ions. This technique can measure positive and negative ion clusters at the same time in six different measuring electrodes. Each measuring electrode detects a different portion of the ion mobility distribution formed within the cell's radioactive source. The pattern recognition used is based on differences in the gas profiles for different compounds. This study shows that an ion mobility spectrometer can be used to monitor Phosdrin from foliage without the need for any time-consuming extraction procedure. The responses for Phosdrin-containing and background (control) samples were easily separated from each other. The responses declined as a function of time in the positive and sum response channels. In addition, the sum of the absolute values of signals at six measuring channels (sum response) were linearly proportional to the concentration of Phosdrin. Just before application (i.e., in background), this value was 41 bits, whereas these values were 10-fold, 11-fold, 8-fold, 6-fold, 5-fold, and 3.5-fold at the time points 4, 8, 11, 24, 50, and 72 hours after the spraying of Phosdrin.

Comparison of intravenous and oral ketoprofen for postoperative pain after adenoidectomy in children.

One hundred children, aged 1-9 yr, undergoing adenoidectomy were randomized to receive ketoprofen 1 mg kg-1 either i.v. with an oral placebo (n = 40) or ketoprofen 1 mg kg-1 orally with an i.v. placebo (n = 40), or both oral and i.v. placebo (n = 20). The study design was prospective and double blind with parallel groups. The pain was assessed at rest and during swallowing using the Maunuksela pain scale (0 = no pain, 10 = worst possible pain) after surgery for 3 h. Fentanyl 0.5 microgram kg-1 i.v. was given for rescue analgesia. Children in the i.v. group needed significantly less doses (1, 1-3; median and 10th/90th percentiles) of rescue analgesic compared with the oral group (2, 1-3; P = 0.024). Of those who needed rescue analgesic, three out of 30 children in the i.v. group required three or more doses of fentanyl compared with 10 out of 28 children in the oral group. There were no differences between the groups with respect to pain scores, operation times, perioperative bleeding or frequency of adverse events.

Pain management after adenoidectomy with ketoprofen: comparison of rectal and intravenous routes.

We compared the efficacy of rectally and intravenously administered ketoprofen for pain management after day-case adenoidectomy. Patients (123 children aged 1-9 yr) were allocated randomly to receive on induction of anaesthesia ketoprofen 25 mg rectally with an i.v. placebo, ketoprofen 25 mg i.v. with a rectal placebo, or placebo both i.v. and rectally. The method of anaesthesia and the operative technique were standardized. Postoperative pain was assessed at rest and during swallowing using the Maunuksela pain scale (0=no pain, 10=worst possible pain). Fentanyl 0.5 microg kg(-1) was given as rescue analgesia. There was no significant difference between the two ketoprofen groups in their requirement for rescue analgesics. However, both the proportion of children needing rescue analgesics [55 of 84 children (65%) vs. 33 of 39 children (84%); difference 19%, 95% confidence interval 4-34%, P=0.029] and the number of rescue analgesic doses [mean 1.2 (SD 1.2) vs. 2.2 (1.4); mean difference 0.9, 95% confidence interval 0.4-1.4, P=0.001] were significantly lower among children receiving ketoprofen than in children receiving placebo. Adverse events, duration of operation, perioperative bleeding, pain scores and time of discharge were similar in the three groups.

Postoperative pain after adenoidectomy in children.

We have investigated if pain intensity or analgesic requirements in hospital predicted pain intensity, pain duration or analgesic requirements at home in 611 children, aged 1-7 yr, after day-case adenoidectomy. We also investigated if ketoprofen 0.3-3.0 mg kg-1, administered pre-emptively i.v. during operation, modified pain at home. In hospital, a prospective, randomized, double-blind, placebo-controlled study design was performed. A standard anaesthetic technique was used in all children and fentanyl i.v. was available for rescue analgesia. After discharge, the study design was open, experimental, prospective and longitudinal. On return home, children were prescribed ketoprofen tablets 5 mg kg-1 day-1. Parents were asked to complete an analgesia diary; non-responders were contacted by telephone. The response rate was 91%. The number of doses of fentanyl given in hospital correlated with pain intensity at home (P < 0.001). There were no other correlations and no pre-emptive effect of ketoprofen.

Intravenous ketoprofen and epidural sufentanil analgesia in children after combined spinal-epidural anaesthesia.

BACKGROUND: Epidural opioid analgesia has become more popular for postoperative pain treatment in children. Epidural opioids are associated with adverse effects such as respiratory depression, excessive sedation, protracted vomiting, urinary retention and pruritus. Following minor surgery, ketoprofen has a synergistic effect with opioids, resulting in an improved analgesia without increase in incidence of adverse effects. To see whether this is also true following major surgery, we compared the effect of i.v. ketoprofen and placebo as an adjuvant to epidural sufentanil analgesia. METHODS: A prospective, randomised, double-blind, placebo-controlled, parallel-group study design was used in 58 children, aged 1-15 years, receiving a standardised combined spinal-epidural anaesthesia. Intravenous ketoprofen or saline was provided as a bolus and a continuous infusion in addition to epidural sufentanil infusion, which was adjusted as clinically required. Epidural bupivacaine was used for rescue analgesia. The study drug infusion was discontinued when pain scores were <3 on a 0-10 scale for 6 h with an epidural sufentanil infusion rate of 0.03 microg kg(-1) h(-1). RESULTS: Children in the ketoprofen group received less rescue analgesia (none/29 vs. 8/29 children in the placebo group). In the ketoprofen group, criteria to discontinue epidural sufentanil were achieved more often (14 vs. 6 children) before the end of the 72 h study period. Less children in the ketoprofen group suffered pruritus (13 vs. 4). The incidence of nausea/retching and vomiting was similar (11 vs. 12) in both groups. CONCLUSION: In this study, ketoprofen as a background analgesic to epidural sufentanil provided improved postoperative analgesia and reduced incidence of adverse effects of the epidural opioid.

Success of pyridostigmine, physostigmine, eptastigmine and phosphotriesterase treatments in acute sarin intoxication.

The acute toxicity of organophosphorus (OP) compounds in mammals is due to their irreversible inhibition of acetylcholinesterase (AChE) in the nervous system, which leads to increased synaptic acetylcholine levels. The protective actions of intravenously (i.v.) administered pyridostigmine, physostigmine, eptastigmine, and an organophosphate hydrolase, phosphotriesterase, in acute sarin intoxication were studied in mice. The acute intragastric (i.g.) toxicity (LD50) of sarin with and without the pretreatments was tested by the up-and-down method. The mice received pyridostigmine (0.06 mg/kg body weight), physostigmine (0.09 mg/kg body weight), the physostigmine derivative eptastigmine (0.90 mg/kg body weight) or phosphotriesterase (104 U/g, 10.7 microg/g body weight) 10 min prior to the i.g. administration of sarin. Physostigmine was also administered with phosphotriesterase. Phosphotriesterase was the most effective antidote in sarin intoxication. The LD50 value for sarin increased 3.4-fold in mice receiving phosphotriesterase. Physostigmine was the most effective carbamate in sarin exposure. The protective ratios of physostigmine and pyridostigmine were 1.5- and 1.2-1.3-fold, respectively. Eptastigmine did not give any protection against sarin toxicity. Both the phosphotriesterase and physostigmine treatments protected the brain AChE activities measured 24 h after sarin exposure. In phosphotriesterase and physostigmine-treated mice, a 4- and 2-fold higher sarin dose, respectively, was needed to cause a 50% inhibition of brain AChE activity. Moreover, the combination of phosphotriesterase-physostigmine increased the LD50 value for sarin 4.3-fold. The animals pretreated with phosphotriesterase-ephysostigmine tolerated four times the lethal dose in control animals, furthermore their survival time was 2-3 h in comparison to 20 min in controls. In conclusion, phosphotriesterase and physostigmine were the most effective treatments against sarin intoxication. However, eptastigmine did not provide any protection against sarin toxicity.

The effect of intravenous ketoprofen on postoperative epidural sufentanil analgesia in children.

UNLABELLED: We compared the effect of IV ketoprofen and placebo as an adjuvant to epidural sufentanil analgesia after major surgery. We used a prospective, randomized, double-blinded, placebo-controlled, parallel-group study design in 54 children aged 1-15 yr who received a standardized anesthetic. Either IV ketoprofen or saline was administered in addition to an epidural sufentanil infusion, which was adjusted as required clinically. The study drug infusions were discontinued when pain scores were <3 on 0-10 scale for 6 h at a sufentanil infusion rate of 0.03 microg x kg(-1) x h(-1). Children in the ketoprofen group had a better analgesic effect, as shown by decreased need for sufentanil (mean [10th-90th percentiles] 8.3 [3.1-15.1] microg/kg vs 12.5 [6.2-18.9] microg/kg; P = 0.002) and earlier possibility to discontinuation of the epidural sufentanil (11 [46%] vs 3 [13%]; P = 0.014) before the end of the 72-h study period. In the ketoprofen group, median (range) pain scores were lower during activity at 24 h (2 [0-5] vs 5 [0-7]; P = 0.01) and at 72 h (0 [0-3] vs 2 [0-6]; P = 0.033), and fewer children had inadequate pain relief during activity at 24 h (0 vs 5; P = 0.037). Children who received ketoprofen required fewer infusion rate adjustments (12 [4-20] vs 17 [6-42]; P = 0.016). In the ketoprofen group, the incidence of desaturation (1 [4%] vs 6 [26%]; P = 0.035) and fever (3 [12%] vs 11 [48%]; P = 0.008) was less than that in the placebo group. We conclude that ketoprofen improved postoperative pain in children. IMPLICATIONS: We compared the effect of the IV nonsteroidal antiinflammatory drug ketoprofen versus placebo as adjuvants to epidural opioid analgesia with sufentanil. The continuous IV nonsteroidal antiinflammatory drug improved pain after major surgery in children receiving an epidural opioid. Although ketoprofen reduced epidural sufentanil requirements, the incidence of opioid-related adverse effects was not changed.

Peroperative treatment with i.v. ketoprofen reduces pain and vomiting in children after strabismus surgery.

BACKGROUND: Strabismus surgery is associated with both pain and vomiting. Ketoprofen is widely used in adults to treat acute pain, but there are only few reports of its use in children. This randomised, double-blind, placebo-controlled, parallel group study was designed to investigate the analgesic effect of i.v. ketoprofen and its effect on the incidence of vomiting in children after day-case strabismus surgery. METHODS: Fifty-nine ASA 1 children, aged 1-12 years, entered the study. After premedication with diazepam and glycopyrronium, anaesthesia was induced with fentanyl and propofol and maintained with isoflurane. After induction the children in the ketoprofen group received 1 mg kg-1 ketoprofen followed by an infusion of 1 mg kg-1 ketoprofen over 2 h. In the placebo group, children received 0.9% saline. The postoperative pain was assessed by the Maunuksela pain score (0 = no pain, 10 = worst possible pain). All children received fentanyl as a rescue analgesic if the Maunuksela score was > or = 3. RESULTS: In the ketoprofen group the number of fentanyl doses was smaller compared to the placebo group (median 1, quartiles (0-2) vs. 2 (1-3), P = 0.047). The children in the ketoprofen group had less pain at 30 min (P = 0.02) and the worst pain observed in the post anaesthesia care unit was lower (3 (0-6) vs. 5 (3-8), P = 0.035). The incidence of vomiting was less in the ketoprofen group compared to the placebo group (17% vs. 41%, P = 0.036). No serious adverse reactions occurred. CONCLUSION: We concluded that ketoprofen administered i.v. during the operation produced analgesia and reduced opioid consumption and the incidence of vomiting in children after strabismus surgery.

Protection of mice against soman by pretreatment with eptastigmine and physostigmine.

Organophosphate (OP) compounds such as the nerve agents sarin, soman and VX are powerful inhibitors of acetylcholinesterases (AChEs), butyrylcholinesterases (BChEs), and carboxylesterases (CaEs) The acute toxicity of OPs is the result of their irreversible binding with AChEs in the nervous system, which elevates the acetylcholine (ACh) levels. In this study the protective actions of intravenously (i.v.), administered eptastigmine and physostigmine in acute soman intoxication were studied in mice. The mice received eptastigmine (0.9 mg/kg body weight) or physostigmine (0.1 mg/kg body weight) 10 min prior to the intraperitoneal (i.p.) administration of soman. To avoid possible signs of poisoning, the animals received atropine 37.5 mg/kg body weight subcutaneously (s.c.) in saline immediately after soman injection. Eptastigmine was the most effective carbamate against soman intoxication. The LD50 value of soman was 0.44 mg/kg, and the protective ratios of eptastigmine and physostigmine were 2.1- and 1.3-fold, respectively. Both eptastigmine and physostigmine had protected AChEs when measured 24 h after soman exposure. In this study, there was no inhibition of microsomal CaEs in soman treated mice. Nonetheless, the role of microsomal CaEs might be more important with prophylaxis at multiple LD50s of soman. In conclusion, these results indicate that eptastigmine treatment given i.v. protects better than physostigmine against soman exposure.

Effect of phenobarbital and beta-naphthoflavone on activities of different rat esterases after paraoxon exposure.

1. The effects of two model inducers of the cytochrome P450 system, phenobarbital (PB) and beta-naphthoflavone (NF), on the toxicity of paraoxon were studied in rats. 2. Paraoxon toxicity was measured by inhibition of brain acetylcholinesterase (AChE) activity. 3. PB treatment did not affect the toxicity of paraoxon, whereas NF increased the inhibition of brain AChE. PB administration slightly increased the activities of some peripheral cholinesterases and carboxylesterases, as well as liver microsomal paraoxonase (Pxase). 4. NF administration, in contrast, decreased the activities of peripheral esterases. Serum Pxase activity was reduced by both inducers. 5. Hepatic CYP2B and CYP1A were markedly induced by PB and NF, respectively. 6. Cytochrome P450 isoenzymes induced by PB or NF seemed not to be critical in the detoxification of paraoxon in vivo. NF caused a general reduction of peripheral esterases, which led to an increase in paraoxon toxicity. 7. The results indicated the great importance of peripheral cholinesterases and carboxylesterases as a detoxifying mechanism of paraoxon. The role of serum paraoxonase was not critical.

Spinal anaesthesia for paediatric day-case surgery: a double-blind, randomized, parallel group, prospective comparison of isobaric and hyperbaric bupivacaine.

We have compared bupivacaine 5 mg ml-1, either isobaric in saline 0.9% or hyperbaric in 8% glucose, for spinal anaesthesia in 100 children, aged 2-115 months, in a double-blind, randomized, parallel group, prospective study. Children were premedicated with diazepam 0.5 mg kg-1 orally. Seventy-two children were sedated before, and 25 children after, lumbar puncture, with either propofol or thiopental (thiopentone). After lumbar puncture in the lateral decubitus position with a 24-27-gauge paediatric spinal needle, isobaric or hyperbaric bupivacaine 5 mg ml-1 was injected in a dose of 0.3-0.5 mg kg-1 using a blinded procedure. Maximum cephalad extent of the block was tested by transcutaneous electrical stimulation. The success rate of the block was greater with hyperbaric bupivacaine (96%) compared with isobaric bupivacaine (82%) (P = 0.025, 95% confidence intervals (CI) 0-28%). Intense motor block was associated with adequate sensory block. Spread and duration of sensory block showed a similar wide scatter in both groups. The highest median level of sensory block was T4 (range T1-12) in the isobaric group and T4 (T1-7) in the hyperbaric group. Times to two segment regression of block were similar: 80 (55-190) min in the isobaric and 80 (30-190) min in the hyperbaric group. Cardiovascular stability was good. Etilefrin was administered to one child to treat hypotension and atropine to one child to treat bradycardia. The study gave an impression of a delayed onset time of spinal block, as most of the nine children who required either fentanyl or a sedative for a mild reaction to skin incision had complete block when transferred to the recovery room after operation. Five children developed a mild, position-dependent headache.

I.v. intraoperative ketoprofen in small children during adenoidectomy: a dose-finding study.

We have investigated if a low dose of ketoprofen (0.3 mg kg-1) i.v., provided as good analgesia with less adverse effects than higher doses (1.0 and 3.0 mg kg-1) in 220 children, aged 1-7 yr, undergoing adenoidectomy, in a prospective, randomized, double-blind, placebo-controlled, parallel group study. The postoperative analgesic effect was notable even after the lowest dose of ketoprofen. However, the higher doses seemed to provide better analgesia with no increase in adverse events or intraoperative bleeding. None of the children experienced postoperative bleeding which would have required intervention or delayed discharge from hospital. This study confirms the efficacy and safety of intraoperative ketoprofen in children during adenoidectomy.

Gender differences in activities of mouse esterase and sensitivities to DFP and sarin toxicity.

1. Gender differences in the toxicity of diisopropylfluorophosphate (DFP; 4.0 mg/kg) and isopropyl methylphosphonofluoridate (sarin; 0.3 mg/kg) were studied in mice. 2. The animals were killed 3 hr after intraperitoneal (IP) injection of the organophosphates (OPs). 3. Although the activity of plasma butyrylcholinesterase (BChE) was two-fold higher and carboxylesterase (CaE) 1.3-fold higher in females than in males, the elevated BChE and CaE activities did not prevent inhibition of the enzyme by OPs in brain. 4. The differences in plasma BChE and CaE activities do not seem to be critical for the detoxification of OPs used in this study.

IV perioperative ketoprofen in small children during adenoidectomy.

We have investigated the analgesic and opioid sparing effect of perioperative i.v. ketoprofen in a randomized, double-blind, placebo-controlled, parallel group study in 164 children, aged 1-7 yr, after adenoidectomy. A standard anaesthetic method was used and all children received fentanyl 1 microgram kg-1 i.v. during induction. Children in the ketoprofen group received ketoprofen 1 mg kg-1 i.v. after induction of anaesthesia followed by an infusion of ketoprofen 1 mg kg-1 over 2 h. Children in the placebo group received 0.9% saline. All children received fentanyl 1 microgram kg-1 i.v. as rescue analgesia. In the ketoprofen group less children required postoperative fentanyl (64% vs 77%, P = 0.006) and the total number of fentanyl doses was smaller compared with the placebo group (mean 1.0 (SD 1.1) (95% confidence intervals (CI) 0.8-1.3) vs 1.5 (1.1) (95% CI 1.2-1.7), P = 0.012). Worst pain observed in the postanaesthesia care unit was also lower in the ketoprofen group both at rest (P = 0.028) and during swallowing (P = 0.001). There were no difference in the number of adverse reactions between the groups. No serious adverse reactions occurred.

Comparison of perioperative ketoprofen 2.0 mg kg-1 with 0.5 mg kg-1 i.v. in small children during adenoidectomy.

We have investigated if ketoprofen 0.5 mg kg-1 i.v. provided as good analgesia with less adverse effects compared with ketoprofen 2.0 mg kg-1 i.v. in 107 children, aged 1-7 yr, after adenoidectomy, in a randomized, double-blind, parallel group study design. A standard anaesthetic method was used and all children received fentanyl 1 microgram kg-1 i.v. during induction. Children in group 2.0 received ketoprofen 2.0 mg kg-1 and children in group 0.5, 0.5 mg kg-1 i.v. during induction. If the child was in pain, fentanyl 1 microgram kg-1 was given i.v. as rescue analgesia. We found that ketoprofen provided good analgesia and only 49% of children required fentanyl in the post-anaesthesia care unit. There were no differences between the groups in the number of fentanyl doses, pain scores or frequency of adverse reactions. No serious adverse reactions occurred.

Phosphotriesterase, pralidoxime-2-chloride (2-PAM) and eptastigmine treatments and their combinations in DFP intoxication.

The protective action of i.v. administered eptastigmine, an organophosphate hydrolase (phosphotriesterase), or pralidoxime-2-chloride (2-PAM) and their combination in acute diisopropylfluorophosphate (DFP) intoxication were evaluated in mice. The mice received the physostigmine derivative, eptastigmine (0.9 mg/kg body wt, i.v.), 10 min prior to the i.p. injection of DFP (1.8 mg/kg body wt). Phosphotriesterase (66 micromol/min x ml/g and 6 microg/g body wt) or 2-PAM (30 mg/kg body wt) were given i.v. 30 min after DFP. The animals also received atropine sc (37.5 mg/kg body wt) immediately after DFP. The cholinesterase (ChE) activities were not protected or reactivated by 2-PAM alone. The ChE activities in brain and plasma were protected by phosphotriesterase. Eptastigmine alone assisted the recovery of the brain ChE activities. Also the combination of eptastigmine-phosphotriesterase protected the brain enzymes. It did not, however, provide any additional protection compared with phosphotriesterase-treatment on its own. In brain, the combination of eptastigmine with 2-PAM resulted in partly restored enzyme activities 24 hr after DFP exposure. In plasma, eptastigmine did not prevent the inhibition of ChE by DFP. However, when it was combined with phosphotriesterase, it significantly promoted the recovery of plasma ChE activity. In lung and in erythrocytes, the various combinations of antidotes caused only minor changes in the ChE activities.

Interspecies differences in enzymes reacting with organophosphates and their inhibition by paraoxon in vitro.

1 Inhibition of cholinesterases (ChE) and carboxylesterases (CaE) by paraoxon (Px) was studied in vitro in the serum, liver, lung and muscle of mouse, guinea pig, rabbit and man (serum only). Moreover, the role of Px hydrolyzing enzyme (Pxase) in the detoxification of Px was studied by inhibiting its activity with EDTA. 2 The ChE and CaE activities as well as their sensitivity to Px varied in different tissues and species. The ChEs were more sensitive than CaEs to Px except in the liver. The CaE activity in human and rabbit sera was low and resistant to Px, indicating that it may have a minor importance for the binding of Px. 3 The Px-inhibited ChEs were spontaneously reactivated in the mouse and rabbit sera during 24 h. In mouse, also the CaE activity was recovered. The presence of EDTA in the incubation medium prevented this reactivation indicating that Pxase takes part in the reactivation process. 4 In rabbit, the serum Pxase activity was very high suggesting a good Px detoxifying capacity of the rabbit serum. 5 The results show that amounts and sensitivities of esterases to OPs in rodents may markedly differ from that in man. Possible species-related differences in the affinity of ChEs and CaEs for OPs and the OP hydrolyzing activity should be taken into the consideration, when animal data are extrapolated to man.

Eptastigmine-phosphotriesterase combination in DFP intoxication.

A novel therapy against organophosphate exposure, the combination of a carbamate eptastigmine and an organophosphate hydrolase (phosphotriesterase) was studied in mice against diisopropylfluorophosphate (DFP) (1.75 mg/kg) exposure. Mice received eptastigmine (0.9 mg/kg; iv) 10 min prior to the ip injection of DFP. Phosphotriesterase (83 U/g body weight) was injected iv 10 min after DFP. Eptastigmine (1.5 mg/kg; iv) inhibited the acetylcholinesterase activities in brain and erythrocytes for a longer time than physostigmine. Eptastigmine caused only minor changes in the behavior and activity of the animals, whereas physostigmine clearly reduced their activity for about 30 min. The eptastigmine pretreatment clearly supplemented the protective effect of phosphotriesterase against DFP: the plasma butyrylcholinesterase activity was doubled and the activity recovered faster than in animals treated with phosphotriesterase alone. In lung, butyrylcholinesterase activity was initially lower after eptastigmine-phosphotriesterase than phosphotriesterase treatment alone. However, the activity returned 24 hr later to normal in eptastigmine-phosphotriesterase-treated groups. With phosphotriesterase only, it recovered only to 75% of the control level. Presumably eptastigmine, by preventing the binding of DFP to cholinesterases, caused an elevation of free DFP levels in body fluids and promoted phosphotriesterase hydrolysis of DFP.

Protection of organophosphate-inactivated esterases with phosphotriesterase.

The protective effect of phosphotriesterase (PTE) on cholinesterase (ChE) and carboxylesterase (CaE) activities was studied in mice. The PTE pretreatment (120 U/g body wt, 9.6 micrograms/g body wt) given i.v. 10 min before diisopropyl fluorophosphate, sarin, or soman variably prevented ChE inhibition in erythrocytes and plasma and CaE in plasma. PTE also protected the brain and lung ChEs against inactivation by organophosphates (OPs). The recovery of the enzymes was dependent on the OP used. Postexposure therapy with PTE, given 1.5 hr after paraoxon, also prevented ChE inhibition in erythrocytes, brain, and lung 24 hr after exposure. The distribution studies with [125I]PTE showed that PTE does not markedly gain access into the central nervous system.