scholarly journals 14C-Psilocin tissue distribution in pregnant rats after intravenous administration

2014 ◽  
Vol 4 (6) ◽  
pp. 232
Author(s):  
Francis Law ◽  
Grace Poon ◽  
Y. C. Chui ◽  
Shao-Xiong He
Keyword(s):  
Half Life ◽  
Wistar Rats ◽  
Urine Samples ◽  
Human Consumption ◽  
Placental Barrier ◽  
Time Curve ◽  
Pregnant Rats ◽  
Elimination Half Life ◽  
Fetal Tissues ◽  
Elimination Half

Background: Many species of hallucinogenic mushrooms have been found in the genus Psilocybe. The main psychoactive chemicals of Psilocybe mushrooms are psilocin and its phosphoryloxy derivative, psilocybin. In addition to its psychedelic effects, psilocybin is an effective agent to lift the mood of depressed patients with terminal cancers.Objective: To study the dispositional kinetics of 14C-psilocin in pregnant rats after intravenous injection, to calculate tissue dose surrogates i.e., tissue 14C concentration and area under the concentration-time curve using the experimental data, to quantify trans-placental passage of psilocin and/or its metabolites, and to identify new psilocin metabolite(s) in rat urine.Methods: A group of 15 pregnant Wistar rats weighing between 0.30-0.36 kg was used in the study. Each rat was given a single dose of 7.5 mg/kg 14C-psilocini.v. Three rats were randomly selected and sacrificed at 0.5, 1.0, 2.0, 4.0, and 8.0 hr post-dosing. The maternal and fetal tissues were quickly removed and the radioactivity in these tissues determined by liquid scintillation counting.In a separate study, urine samples were collected from 6 male Wistar rats after administering 15 mg/kg of unlabeled psilocin i.p. The urine samples were collected and extracted by chloroform-methanol (9:1 v/v) and analyzed using a gas chromatograph/mass spectrometer.Results: 14C-Psilocin crossed the placental barrier of pregnant rats readily after i.v. administration; maternal tissue 14C concentrations were found to be much higher than those in fetal tissues. The areas under the curve for maternal tissues also were much higher than the fetal tissues. In general, maternal tissues could be divided into the fast eliminating organ group, which included the brain (elimination half-life <13 hr) and the slow eliminating organ group, which included all fetal tissues (elimination half-life >13 hr). A new psilocin metabolite tentatively identified as dihydroxyindoleacetic acid was found in the urine.Conclusion: Our study showed that psilocin readily crossed the placental and blood-brain barriers of pregnant rats. Because psilocin was eliminated slowly from the fetal tissues of rats, human consumption of magic mushrooms should be avoided during pregnancy. Key words: magic mushrooms, psilocin, placental barrier, pregnant rats

scholarly journals Interaction between Grapefruit Juice and Praziquantel in Humans

2002 ◽  
Vol 46 (5) ◽  
pp. 1614-1616 ◽  
Author(s):  
Nelly Castro ◽  
Helgi Jung ◽  
Roberto Medina ◽  
Dinora González-Esquivel ◽  
Mario Lopez ◽  
...  
Keyword(s):  
Water Treatment ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Half Life ◽  
Maximum Concentration ◽  
Grapefruit Juice ◽  
Time Curve ◽  
Elimination Half Life ◽  
Concentration Time ◽  
Elimination Half

ABSTRACT After a single oral dose of praziquantel with 250 ml of grapefruit juice, the area under the concentration-time curve and the maximum concentration in plasma of praziquantel (C max) were significantly increased (C max for water treatment, 637.71 ± 128.5 ng/ml; and C max for grapefruit juice treatment, 1,037.65 ± 305.7 ng/ml, P < 0.05). No statistically significant differences were found in the time to maximum concentration of drug in plasma or elimination half-life.

Phase I Trial of Carmustine Plus O6-Benzylguanine for Patients With Recurrent or Progressive Malignant Glioma

2000 ◽  
Vol 18 (20) ◽  
pp. 3522-3528 ◽  
Author(s):  
Henry S. Friedman ◽  
James Pluda ◽  
Jennifer A. Quinn ◽  
Reginald B. Ewesuedo ◽  
Lina Long ◽  
...  
Keyword(s):  
Phase I ◽  
Malignant Glioma ◽  
Half Life ◽  
Phase I Trial ◽  
Maximum Tolerated Dose ◽  
Time Curve ◽  
Elimination Half Life ◽  
Major Mechanism ◽  
Elimination Half ◽  
The Mean

PURPOSE: The major mechanism of resistance to alkylnitrosourea therapy involves the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT), which removes chloroethylation or methylation damage from the O6 position of guanine. O6-benzylguanine (O6-BG) is an AGT substrate that inhibits AGT by suicide inactivation. We conducted a phase I trial of carmustine (BCNU) plus O6-BG to define the toxicity and maximum-tolerated dose (MTD) of BCNU in conjunction with the preadministration of O6-BG with recurrent or progressive malignant glioma. PATIENTS AND METHODS: Patients were treated with O6-BG at a dose of 100 mg/m2 followed 1 hour later by BCNU. Cohorts of three to six patients were treated with escalating doses of BCNU, and patients were observed for at least 6 weeks before being considered assessable for toxicity. Plasma samples were collected and analyzed for O6-BG, 8-oxo-O6-BG, and 8-oxoguanine concentration. RESULTS: Twenty-three patients were treated (22 with glioblastoma multiforme and one with anaplastic astrocytoma). Four dose levels of BCNU (13.5, 27, 40, and 55 mg/m2) were evaluated, with the highest dose level being complicated by grade 3 or 4 thrombocytopenia and neutropenia. O6-BG rapidly disappeared from plasma (elimination half-life = 0.54 ± 0.14 hours) and was converted to a longer-lived metabolite, 8-oxo-O6-BG (elimination half-life = 5.6 ± 2.7 hours) and further to 8-oxoguanine. There was no detectable O6-BG 5 hours after the start of the O6-BG infusion; however, 8-oxo-O6-BG and 8-oxoguanine concentrations were detected 25 hours after O6-BG infusion. The mean area under the concentration-time curve (AUC) of 8-oxo-O6-BG was 17.5 times greater than the mean AUC for O6-BG. CONCLUSION: These results indicate that the MTD of BCNU when given in combination with O6-BG at a dose of 100 mg/m2 is 40 mg/m2 administered at 6-week intervals. This study provides the foundation for a phase II trial of O6-BG plus BCNU in nitrosourea-resistant malignant glioma.

scholarly journals Azelastine and suplatast shorten the distribution half-life of IgE in rats

2002 ◽  
Vol 11 (1) ◽  
pp. 61-64 ◽  
Author(s):  
Kazuhiko Hanashiro ◽  
Yoshihiro Tokeshi ◽  
Toshiyuki Nakasone ◽  
Masanori Sunagawa ◽  
Mariko Nakamura ◽  
...  
Keyword(s):  
Immunosorbent Assay ◽  
Rate Constants ◽  
Half Life ◽  
Wistar Rats ◽  
Immunoglobulin E ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pharmacokinetic Parameters ◽  
Distilled Water ◽  
Elimination Half Life ◽  
Elimination Half

We aim to clarify whether suplatast and azelastine (anti-allergic drugs) can shorten the half-life of immunoglobulin E (IgE) in the circulating blood. Thirty Wistar rats were divided into six groups. Distilled water or anti-allergic drugs were given orally for 6 days after the first sensitization. Two milligrams of monoclonal dinitrophenyl (DNP)-specific rat IgE was administered to the rats, which had been given suplatast or azelastine orally. The level of DNP-specific rat IgE in the serum was estimated by IgE-capture enzyme-linked immunosorbent assay, and the turnover of IgE was analyzed from its pharmacokinetic parameters. The elimination half-life of rat IgE was about 12 h irrespective of the sensitized state. The intercompartmental rate constants (KctandKtc) in the suplatast-administered or azelastine-administered group were larger than those of the distilled water-administered group under non-sensitized conditions. These findings suggested that the anti-allergic drugs used in the present study facilitated the excretion of IgE from the circulation in rats.

scholarly journals Die kliniese farmakologie van hirudien - 'n nuwe antistolmiddel

1992 ◽  
Vol 11 (2) ◽  
pp. 59-61
Author(s):  
B. H. Meyer ◽  
F. O. Muller ◽  
H. G. Luus ◽  
N. De la Rey
Keyword(s):  
Linear Relationship ◽  
Partial Thromboplastin Time ◽  
Half Life ◽  
Time Curve ◽  
Subcutaneous Injections ◽  
Elimination Half Life ◽  
Elimination Half

Increasing doses of 0,05, 0,1, 0,15 and 0,2 mg/kg of rDNA hirudin, a new anti-coagulant, were given subcutaneously to 20 volunteers (5 per dose) in order to investigate the tolerance and pharmacokinetics of the compound and its effects on coagulation. Hirudin was tolerated very well, the elimination half-life after subcutaneous injections is about 2 hours, about 40% of a given dose is excreted through the kidneys, and an excellent linear relationship was found between the area under the plasma concentration­ time curve and the dose. Hirudin increased partial thromboplastin time in a dose-related fashion.

Plasma pharmacokinetics and pharmacodynamics of a new prodrug N-l-leucyldoxorubicin and its metabolites in a phase I clinical trial.

1992 ◽  
Vol 10 (12) ◽  
pp. 1897-1906 ◽  
Author(s):  
J de Jong ◽  
G J Geijssen ◽  
C N Munniksma ◽  
J B Vermorken ◽  
W J van der Vijgh
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Half Life ◽  
Maximum Tolerated Dose ◽  
Phase I Clinical Trial ◽  
Major Constituent ◽  
Hematologic Toxicity ◽  
Time Curve ◽  
Elimination Half Life ◽  
Elimination Half

PURPOSE N-l-leucyldoxorubicin (Leu-Dox) was developed as a prodrug of doxorubicin (Dox) to circumvent the cardiotoxicity associated with repeated administration of Dox. Our purpose was to assess the pharmacokinetics of Leu-Dox, Dox, doxorubicinol (Dol) and four other metabolites for pharmacokinetically guided dose-escalation and to verify the prodrug character of Leu-Dox. PATIENTS AND METHODS Blood and urine of 14 patients were sampled during the phase I clinical trial and analyzed by high-performance liquid chromatography. Dose levels of Leu-Dox ranged from 18 mg/m2 to 225 mg/m2, the maximum-tolerated dose (MTD). Hematologic parameters were monitored regularly in each patient. RESULTS Leu-Dox was rapidly distributed (half-life at alpha phase [t1/2 alpha] = 2.5 +/- 0.6 minutes) followed by a biphasic elimination (half-life at beta phase [t1/2 beta] = 17.4 +/- 7.3 minutes; half-life at gamma phase [t1/2 gamma] = 1.5 +/- 0.5 hours), as measured over the first 12 hours after administration. In three patients, in whom Leu-Dox was found in the plasma for up to 48 hours after injection, a final elimination half-life (t1/2,elim) of 16 hours was observed. The t1/2,elim of Leu-Dox was short (0.6 to 16.5 hours) compared with the t1/2,elim of Dox (38 +/- 11 hours). The mean residence time and apparent volume of distribution were 23 +/- 5 minutes and 19 +/- 6 L/m2, respectively. Only 1.5% to 5% of the dose was excreted in the urine over 48 hours, with Dox as major constituent. Dox was rapidly formed, reaching its maximum concentration within 10 minutes after the end of Leu-Dox infusion. Areas under the plasma concentration versus time curve (AUC infinity, mean +/- SD, n = 16) of Leu-Dox, Dox, and Dol were 115 +/- 27 mumol.min/L, 41 +/- 12 mumol.min/L, and 33 +/- 14 mumol.min/L after a dose of 60 mg/m2 Leu-Dox (= 86 mumol/m2). After the same molar dose of Dox (50 mg/m2 = 86 mumol/m2), the AUC infinity of Dox was 179 mumol.min/L, indicating that Leu-Dox was converted into Dox for 23% in the plasma compartment. The AUCs infinity of Leu-Dox, Dox, and Dol increased linearly with the dose. Negligible AUCs were observed for the other four metabolites. The AUCs infinity of Leu-Dox and Dox at the MTD (517 and 145 mumol.min/L, respectively) were lower than those in mice at the LD10 (1,930 and 798 mumol.min/L, respectively), which means that the MTD could not be predicted from the preclinical pharmacokinetics in mice. Hematologic toxicity, especially the WBC count, appeared to correlate much better with the AUC of Dox (r = .91) than with the AUC of Leu-Dox (r = .74), thus confirming the prodrug character of Leu-Dox. CONCLUSIONS Dox is rapidly formed from Leu-Dox, and seems causative in the observed myelotoxicity. The MTD could not be predicted from the AUC at the LD10 in mice.

Influence of concomitant drugs on methadone elimination half-life in patients under a maintenance treatment

2001 ◽  
Vol 6 (2) ◽  
pp. 171-176 ◽  
Author(s):  
A. C. S. Lucas ◽  
A. M. Bermejo ◽  
M. J. Tabernero ◽  
P. FernÁNdez ◽  
P. CÁMpora
Keyword(s):  
Half Life ◽  
Maintenance Treatment ◽  
Elimination Half Life ◽  
Elimination Half

scholarly journals Pharmacodynamics of a Long-Acting Echinocandin, CD101, in a Neutropenic Invasive-Candidiasis Murine Model Using an Extended-Interval Dosing Design

2017 ◽  
Vol 62 (2) ◽  
Author(s):  
Alexander J. Lepak ◽  
Miao Zhao ◽  
Brian VanScoy ◽  
Paul G. Ambrose ◽  
David R. Andes
Keyword(s):  
Invasive Candidiasis ◽  
Half Life ◽  
Intraperitoneal Administration ◽  
Time Curve ◽  
Content Type ◽  
Elimination Half ◽  
Dosing Regimens ◽  
Dosing Strategies ◽  
Long Acting

ABSTRACT Echinocandins are important in the prevention and treatment of invasive candidiasis but limited by current dosing regimens that include daily intravenous administration. The novel echinocandin CD101 has a prolonged half-life of approximately 130 h in humans, making it possible to design once-weekly dosing strategies. The present study examined the pharmacodynamic activity of CD101 using the neutropenic invasive candidiasis mouse model against select Candida albicans (n = 4), C. glabrata (n = 3), and C. parapsilosis (n = 3) strains. The CD101 MIC ranged from 0.03 to 1 mg/liter. Plasma pharmacokinetic measurements were performed using uninfected mice after intraperitoneal administration of 1, 4, 16, and 64 mg/kg. The elimination half-life was prolonged at 28 to 41 h. Neutropenic mice were infected with each strain by lateral tail vein injection, treated with a single dose of CD101, and monitored for 7 days, at which time the organism burden was enumerated from the kidneys. Dose-dependent activity was observed for each organism. The pharmacokinetic/pharmacodynamic (PK/PD) index of the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC index) correlated well with efficacy (R 2, 0.74 to 0.93). The median stasis 24-h free-drug AUC/MIC targets were as follows: for C. albicans, 2.92; for C. glabrata, 0.07; and for C. parapsilosis, 2.61. The PK/PD targets for 1-log10 kill endpoint were 2- to 4-fold higher. Interestingly, the aforementioned PK/PD targets of CD101 were numerically lower for all three species than those of other echinocandins. In summary, CD101 is a promising, novel echinocandin with advantageous pharmacokinetic properties and potent in vivo pharmacodynamic activity.

Lactic Acidosis, Hyperglycaemia and Convulsions following Nalidixic Acid Overdosage

1984 ◽  
Vol 3 (3) ◽  
pp. 239-243 ◽  
Author(s):  
P.J.A. Leslie ◽  
R.J. Cregeen ◽  
A.T. Proudfoot
Keyword(s):  
Plasma Concentration ◽  
Lactic Acidosis ◽  
Nalidixic Acid ◽  
Half Life ◽  
Abnormal Behaviour ◽  
Elimination Half Life ◽  
Elimination Half

1 A woman survived ingestion of 32 g nalidixic acid despite developing lactic acidosis, hyperglycaemia, convulsions and abnormal behaviour. 2 The maximum recorded plasma concentration of nalidixic acid was 185 mg/l and the elimination half-life was 3.2 h. 3 Carboxy-nalidixic acid was demonstrated in the plasma. 4 Previously reported cases of nalidixic acid overdosage are reviewed.

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