Toxicological Studies in a Distalgesic Addict

1986 ◽  
Vol 5 (3) ◽  
pp. 207-210 ◽  
Author(s):  
I. Roberts ◽  
R. J. Flanagan ◽  
J. Strang ◽  
L. F. Prescott
Keyword(s):  
Peak Plasma ◽  
Plasma Concentrations ◽  
High Plasma ◽  
Withdrawal Period ◽  
Total Recovery ◽  
Hepatocellular Damage ◽  
Elimination Half ◽  
Toxicological Studies ◽  
Kinetics Of ◽  
Very High

1 The disposition and kinetics of paracetamol, dextropropoxyphene and their metabolites were investigated in an addict who claimed to be taking 80–100 Distalgesic tablets daily regularly. 2 Plasma concentrations of paracetamol, dextropropoxyphene and their principal metabolites were measured after an oral dose of 15 Distalgesic tablets. 3 The absorption of paracetamol and dextropropoxyphene was rapid with peak plasma concentrations at 15 and 30 min respectively. The elimination half-life for paracetamol was 2.3 h. Nordextropropoxyphene remained at steady state with very high plasma concentrations (5 mg/l). The urinary excretion of paracetamol and metabolites was not abnormal. The total recovery of paracetamol was only 31% of the dose. 4 Apart from raised plasma γ-glutamyltransferase activity there was no biochemical evidence for paracetamol-induced hepatocellular damage despite ingestion of 97.5 g of paracetamol over the 11 days of the withdrawal period.

Propranolol in Children: Safety-Toxicity

PEDIATRICS ◽  
1982 ◽  
Vol 70 (1) ◽  
pp. 30-31
Author(s):  
Michael Artman ◽  
Mitch Grayson ◽  
Robert C. Boerth
Keyword(s):  
Heart Rate Response ◽  
Plasma Concentrations ◽  
Caloric Intake ◽  
High Plasma ◽  
Intravenous Glucose ◽  
First Case ◽  
Acute Ingestion ◽  
Pharmacologic Effect ◽  
Propranolol Therapy ◽  
Very High

Four hours after acute ingestion of 400 to 1,200 mg of propranolol by a healthy, 3-year-old boy, his plasma concentration of propranolol was 2,289 ng/ml. The only pharmacologic effect observed was a diminished heart rate response to crying and activity. In a second case, a 4-year-old boy on chronic propranolol therapy for renovascular hypertension had a hypoglycemic seizure when solid food was refused for three days because of an oral wound. The hypoglycemia was easily managed with intravenous glucose, and there were no sequelae. The first case alludes to the safety of propranolol in a healthy child even with very high plasma concentrations. The second case suggests the necessity of anticipating and avoiding hypoglycemia that can develop in children on chronic propranolol therapy when caloric intake is impaired.

scholarly journals Pharmacokinetic and Pharmacodynamic Evaluation of Marbofloxacin in Pig against Korean Local Isolates ofActinobacillus pleuropneumoniae

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Md. Akil Hossain ◽  
Hae-chul Park ◽  
Kyunghun Jeong ◽  
Yang ho Jang ◽  
Dae Gyun Kim ◽  
...  
Keyword(s):  
Body Weight ◽  
Ex Vivo ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Antibacterial Activities ◽  
Time Intervals ◽  
Concentration Time ◽  
Elimination Half ◽  
The Mean

The pharmacokinetics of marbofloxacin in pigs after intravenous (i.v.), intramuscular (i.m.), and peroral (p.o.) administration and pharmacokinetic/pharmacodynamic indices of this drug against Korean local isolates ofActinobacillus pleuropneumoniaewere determined in this study. Marbofloxacin (2.50 mg/kg of body weight) was administered, and blood samples were collected with designated time intervals. Plasma-extracted marbofloxacin was injected into the LC-MS/MS system. The in vitro and ex vivo antibacterial activities of marbofloxacin were evaluated against 20 isolates ofA. pleuropneumoniae. The mean peak plasma concentrations (Cmax) after i.v., i.m., and p.o administration were2.60±0.10,2.59±0.12, and2.34±0.12 µg/mL at0.25±0.00,0.44±0.10, and1.58±0.40 h, respectively. The area under the plasma concentration-time curves (AUC0–24) and elimination half-lives were24.80±0.90,25.80±1.40, and23.40±5.00 h·μg/mL and8.60±0.30,12.80±1.10, and8.60±0.00 h, for i.v., i.m., and p.o. administration, correspondingly. The AUC0–24/MICs of marbofloxacin after i.v., i.m., and p.o. administration were253.86±179.91,264.1±187.16, and239.53±169.75 h, respectively. TheCmax/MIC values were26.58±18.84,26.48±18.77, and23.94±16.97, and T>MICs were42.80±1.01,36.40±1.24, and38.60±1.18 h, after i.v., i.m., and p.o. administration, respectively. Thus, marbofloxacin dosage of 2.50 mg/kg of body weight by i.v., i.m., and p.o. administration with 24 h dosing interval will provide effective treatment for the infection of pig byA. pleuropneumonia.

Metabolic Aspects of Hypothermia in the Elderly

1980 ◽  
Vol 59 (1) ◽  
pp. 19-27 ◽  
Author(s):  
H. B. Stoner ◽  
K. N. Frayn ◽  
R. A. Little ◽  
C. J. Threlfall ◽  
D. W. Yates ◽  
...  
Keyword(s):  
Amino Acids ◽  
Ketone Bodies ◽  
Plasma Concentrations ◽  
The Elderly ◽  
High Plasma ◽  
Active Involvement ◽  
Esterified Fatty Acids ◽  
Lipid Metabolites ◽  
High Concentrations ◽  
Very High

1. Plasma concentrations of glucose, lactate, amino acids, non-esterified fatty acids, glycerol, ketone bodies, insulin and cortisol were measured in 43 elderly patients with hypothermia. In 15 of these patients forearm arteriovenous differences were also measured. Core temperatures ranged from 25.9 to 35.5°C. 2. The metabolic state was of mobilization of glycogen and triacylglycerol stores, with high plasma concentrations of lactate and lipid metabolites. The plasma concentration of glucose was raised in those with hypothermia of a short duration (<6 h). In other patients it was low in those with core temperatures around 30°C, but below this temperature it was variable and often high. Concentrations of other metabolites or hormones were not related to core temperature. 3. Plasma concentrations of cortisol were high and positively correlated with those of lactate and glycerol, suggesting active involvement in stimulation of muscle glycogenolysis and of lipolysis. 4. Plasma concentrations of insulin ranged from very low to very high and appeared to depend on the concentrations of both glucose and alanine. 5. Arteriovenous differences were generally small. There was peripheral release of lactate and of amino acids but no overall peripheral uptake of glucose. In nine out of 15 patients there was a significant peripheral release of glucose. 6. No differences in metabolism were observed between patients where the hypothermia appeared accidental and those with an obvious precipitating illness, despite a significantly lower mortality in the former group. 7. It was concluded that therapy should primarily involve rewarming of patients by physical means, without metabolic intervention.

Oral Bioavailability of Candesartan Cilexetil Suspension

2007 ◽  
Vol 23 (5) ◽  
pp. 270-274 ◽  
Author(s):  
Renli Teng ◽  
Anna-Carin Hansson ◽  
Inger Börjesson
Keyword(s):  
Candesartan Cilexetil ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Relative Bioavailability ◽  
Maximum Plasma ◽  
Open Label ◽  
Serious Adverse Events ◽  
Time To Peak ◽  
Period 2 ◽  
Elimination Half

Background: Candesartan cilexetil is a prodrug that is converted to candesartan during absorption from the gastrointestinal tract. Candesartan is a potent, orally active, specific angiotensin II type 1 receptor antagonist that has become a well-accepted treatment for hypertension. Pediatric patients often require alternative dosage forms, as candesartan cilexetil is not yet commercially available as a liquid formulation. Objective: To determine the relative bioavailability of candesartan by comparing a candesartan cilexetil tablet (reference formulation) with an oral candesartan cilexetil suspension (test formulation). Methods: In an open-label, randomized, 2 period, 2 treatment crossover study, 24 healthy volunteers were given a 32 mg candesartan cilexetil tablet and a 32 mg candesartan cilexetil suspension with a 7 day washout period between treatments. Results: Pharmacokinetic analyses showed that the mean relative bioavailability of the candesartan cilexetil commercial 32 mg tablet compared with the suspension of 32 mg candesartan cilexetil was 93%. The 90% CIs of the plasma AUC for the tablet versus suspension (0.861 and 0.998, respectively) were well within the bioequivalence criteria of 80–125%. Administration of candesartan cilexetil suspension was associated with a 17% increase in the maximum plasma concentration (Cmax) relative to the tablet administration (643 vs 523 nM/L, respectively). The 90% CIs on the ratio of mean Cmax for the tablet and suspension were 0.738 and 0.914, respectively. Mean time to peak plasma concentrations (tmax) after suspension administration was 3.1 hours, whereas the tablet resulted in a mean tmax of 3.9 hours. No significant differences in elimination half-life were observed between the 2 formulations. Both formulations were well tolerated, and no serious adverse events were reported. Conclusions: These results demonstrate that administration of candesartan cilexetil suspension achieves an extent of absorption and tolerability that is comparable with those of orally administered candesartan cilexetil tablets.

HIGH CORTICOSTEROID LEVELS IN PLASMA OF ADULT AND FOETAL WEDDELL SEALS (LEPTONYCHOTES WEDDELLI)

1979 ◽  
Vol 90 (4) ◽  
pp. 718-726 ◽  
Author(s):  
G. C. Liggins ◽  
J. T. France ◽  
B. S. Knox ◽  
W. M. Zapol
Keyword(s):  
Lean Body Mass ◽  
Body Mass ◽  
Turnover Rate ◽  
Binding Capacity ◽  
Plasma Concentrations ◽  
High Plasma ◽  
Affinity Constant ◽  
Weddell Seals ◽  
Very High ◽  
Main Factor

ABSTRACT Pregnant and non-pregnant Weddell seals and foetuses were found to have very high plasma concentrations of corticosteroids (1–7 μmol/l) that were unaffected by stress. Cortisol comprised most of the corticosteroid in the adult but only 50 % of that in the foetus. The affinity constant (4.30–5.53 × 107 l/mol) and specificity of CBG and the MCR (4.5 l/d/kg lean body mass) in adult seals were similar to those of Man. The binding capacity of CBG (1.48–1.86 μmol/l) which is approximately three times that of Man contributed to the high plasma corticosteroid concentrations but the main factor was the cortisol turnover rate of 3670 μmol/d (1.3 g/d) which is the highest value reported in any species.

Phase I Clinical and Pharmacologic Trial of Intravenous Estramustine Phosphate

2002 ◽  
Vol 20 (4) ◽  
pp. 1115-1127 ◽  
Author(s):  
Gary Hudes ◽  
Naomi Haas ◽  
Gwen Yeslow ◽  
Thomas Gillon ◽  
Per Olov Gunnarsson ◽  
...  
Keyword(s):  
Peak Plasma ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Maximum Tolerated Dose ◽  
Volume Of Distribution ◽  
High Dose ◽  
Weekly Dose ◽  
Estramustine Phosphate ◽  
Active Metabolites ◽  
Elimination Half

PURPOSE: To determine the dose-limiting toxicities, maximum-tolerated dose, and pharmacokinetics of intravenous estramustine phosphate (IV EMP). PATIENTS AND METHODS: A total of 31 patients with hormone-refractory prostate cancer received IV EMP as a 30- to 90-minute infusion weekly (n = 28) or for 3 consecutive days followed by a single weekly dose (n = 3). IV EMP dose was escalated from 500 to 3,000 mg/m2. Pharmacokinetics of EMP and the metabolites estramustine (EaM), estromustine (EoM), estradiol, and estrone were assessed after weeks 1 and 4 of treatment. RESULTS: The initial IV EMP infusion caused perineal discomfort that was ameliorated by lengthening the infusion time. Other common toxicities were grade 1 to 2 hepatotoxicity, nausea or vomiting, and fatigue or malaise. Lower-extremity thrombosis occurred in one patient, and two others developed upper-extremity thrombosis associated with venous infusion catheters. Dose-limiting fatigue and hypotension occurred at 3,000 mg/m2, and cumulative fatigue developed after multiple cycles at 2,500 mg/m2. Mean EMP clearance, estimated steady-state volume of distribution, and elimination half-life were 3.7 L/h, 10.6 L, and 3.7 hours, respectively. Variability of EMP clearance was 21%, and variation in area under the curve per dose for the metabolites was 28% to 36%. Elimination half-lives of EoM and EaM were 110 hours and 64 hours, and peak plasma concentrations of these active metabolites exceeded 10 μmol/L after IV EMP doses ≥ 2,000 mg/m2. CONCLUSION: High-dose IV EMP can be administered safely as a weekly short infusion to patients with HRPC. High peak concentrations of active metabolites after IV EMP may provide an advantage over oral EMP in antimicrotubule drug combinations.

Oral Pharmacokinetics of Fluazifop-Butyl in Human Volunteers

1991 ◽  
Vol 10 (1) ◽  
pp. 39-43 ◽  
Author(s):  
B.H. Woollen ◽  
T.B. Hart ◽  
P.L. Batten ◽  
W.J.D. Laird ◽  
D.S. Davies ◽  
...  
Keyword(s):  
Body Weight ◽  
Active Ingredient ◽  
Half Life ◽  
Pharmacokinetic Model ◽  
Serum Proteins ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Elimination Half ◽  
Human Volunteers ◽  
Oral Pharmacokinetics

1 Fluazifop-butyl, the active ingredient of FUSILADE, a selective herbicide, was administered orally to three male volunteers at a dose level of 0.07 mg kg-1 body weight. Over a period of 6 d between 80 and 93% of the dose was excreted in urine as the metabolite fluazifop, the majority within the first 24 h. Peak plasma concentrations of fluazifop occurred 1-2.5 h after administration. 2 The elimination of fluazifop from plasma and urine can be described by a one-compartment pharmacokinetic model and the elimination half-life was estimated from blood and urine data to be within the range 9-37 h. Fluazifop was found to bind to serum proteins. 3 The study indicates that the amount of fluazifop-butyl absorbed in exposed persons can be assessed by measuring fluazifop concentrations in urine.

Azithromycin: An Assessment of Its Pharmacokinetics and Therapeutic Potential in CAPD

2001 ◽  
Vol 21 (4) ◽  
pp. 372-377 ◽  
Author(s):  
James R. Kent ◽  
Michael K. Almond ◽  
Soraya Dhillon
Keyword(s):  
Peritoneal Dialysis ◽  
Half Life ◽  
Therapeutic Potential ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Future Research ◽  
Renal Unit ◽  
Elimination Half Life ◽  
Elimination Half ◽  
The Mean

Background Azithromycin is an azalide antibiotic with a similar antibacterial spectrum to erythromycin but with greater gram-negative activity. Azithromycin displays a favorable pharmacokinetic profile, with improved absorption and higher sustained tissue concentrations compared with erythromycin. This results in a prolonged elimination half-life, suggesting a potential for treating continuous ambulatory peritoneal dialysis (CAPD) peritonitis. Objective This study aimed to define the potential role of azithromycin in treating CAPD peritonitis. Design The pharmacokinetics and peritoneal dialysis (PD) clearance of azithromycin were studied following a single 500-mg oral dose of azithromycin. Blood and dialysate samples were taken over a 10-day period and assayed using high-pressure liquid chromatography. Setting The study took place within the Renal Unit at Southend Hospital NHS Trust, a district general hospital in the United Kingdom. Patients Eight patients with oliguric end-stage renal failure without peritonitis maintained on CAPD (3 x 2 L/day). Results Peak plasma concentrations occurred at 2 -3 hours with 0.35 - 1.35 mg/mL (mean 0.75). The mean elimination half-life was 84.55 hrs, and plasma clearance was 21.93 L/hour. This compares with values of greater than 40 hours and 40.8 L/hour reported in healthy volunteers. After 8 hours, the mean dialysate concentration was 0.07 mg/mL; PD clearance was 0.06 L/hr. Conclusion Azithromycin is not substantially removed by CAPD in the absence of peritonitis and cannot be recommended for widespread use in this setting at present. However, the successful use of azithromycin in CAPD peritonitis, due possibly to an intracellular drug transport mechanism, has been reported. Future research should address this possibility.

Pharmacokinetics of Standard (Lithicarb) and Sustained-Release (Priadel) Lithium Carbonate Preparations in Patients

1982 ◽  
Vol 16 (1) ◽  
pp. 64-68 ◽  
Author(s):  
G. F. S. Johnson ◽  
G. E. Hunt ◽  
J. Lewis ◽  
B. St. George
Keyword(s):  
Sustained Release ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Lithium Carbonate ◽  
High Plasma ◽  
Level Curves ◽  
Time To Peak ◽  
Release Preparation ◽  
Daily Dose ◽  
Excretion Rates

Equivalent oral dosages (800 mg, 21-6 mmol) of a standard (Lithicarb) and a sustained-release (Priadel) lithium carbonate preparation were administered to six patients receiving lithium maintenance treatment using a randomized cross-over design. There were no significant differences in the two preparations for 24 hour plasma level curves, 24 hour bioavailability, peak plasma concentrations (Cmax), time to peak plasma concentrations (Tmax) or urinary excretion rates. These results are in agreement with a previous study using Priadel in healthy volunteers, and indicate that Priadel is a delayed-release, rather than a true sustained-release preparation. In order to maintain therapeutic plasma levels and to minimise adverse effects that may occur with high plasma lithium levels, Priadel needs to be administered in divided dosages rather than as a single daily dose.

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