Pharmacokinetics and Therapeutic Efficacy of Haloperidol Decanoate after Loading Dose Administration

1986 ◽  
Vol 148 (5) ◽  
pp. 560-566 ◽  
Author(s):  
H. De Cuyper ◽  
J. Bollen ◽  
H. M. van Praag ◽  
D. Verstraeten
Keyword(s):  
Plasma Level ◽  
Open Study ◽  
Oral Treatment ◽  
Oral Dosage ◽  
Loading Dose ◽  
Haloperidol Decanoate ◽  
Dose Administration ◽  
The Third ◽  
Stable Plasma ◽  
Depot Injections

For this open study, we selected 21 chronic psychotic female in-patients (16 of them schizophrenics) who were being maintained on oral neuroleptics. After a wash-out period, they were treated by intramuscular depot injections of haloperidol decanoate, once a month for four months. The dose was calculated from the previous oral dosage, and the amount of the first injection was double that of the three following injections. Relatively stable plasma levels of haloperidol were achieved with the first injection, and corresponded to those observed with oral medication. A very significant correlation was found between plasma level and the dose administered, but not between plasma level and therapeutic effect. The clinical condition of about two-thirds of the patients remained unchanged or improved, compared with the period of oral treatment. During the first two months of treatment, there was more rigidity and tremor, but from the third month, the extrapyramidal symptoms were less pronounced than during the period of oral neuroleptics.

scholarly journals In Vivo Efficacy of VT-1129 against Experimental Cryptococcal Meningitis with the Use of a Loading Dose-Maintenance Dose Administration Strategy

2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Xin Xu ◽  
Amy Wang ◽  
Laura K. Najvar ◽  
Edward P. Garvey ◽  
...  
Keyword(s):  
Cryptococcal Meningitis ◽  
Maintenance Dose ◽  
Oral Treatment ◽  
Loading Dose ◽  
Dose Administration ◽  
Once Daily ◽  
Content Type ◽  
Fungal Burden ◽  
Dose Strategy

ABSTRACT VT-1129 is a novel fungal enzyme-specific Cyp51 inhibitor with potent cryptococcal activity. Because of its long half-life (>6 days in mice) and our desire to quickly reach potent efficacy, we evaluated a VT-1129 loading dose-maintenance dose strategy against cryptococcal meningitis. VT-1129 plasma and brain pharmacokinetics were first studied in healthy mice, and these data were used to model loading dose-maintenance dose regimens to generate different steady-state concentrations. Mice were inoculated intracranially with Cryptococcus neoformans, and oral treatment began 1 day later. Treatment consisted of placebo or one of three VT-1129 loading dose-maintenance dose regimens, i.e., loading dose of 1, 3, or 30 mg/kg on day 1, followed by once-daily maintenance doses of 0.15, 0.5, or 5 mg/kg, respectively. In the fungal burden arm, therapy continued for 14 days and brains were collected on day 15 for fungal burden assessments. In the survival arm, treatment continued for 10 days, after which mice were monitored without therapy until day 30. VT-1129 plasma and brain concentrations were also measured. All VT-1129 doses significantly improved survival and reduced fungal burdens, compared to placebo. VT-1129 plasma and brain levels correlated with fungal burden reductions (R2 = 0.72 and R2 = 0.67, respectively), with a plasma concentration of 1 μg/ml yielding a reduction of ∼5 log10 CFU/g. With the highest loading dose-maintenance dose regimen, fungal burdens were undetectable in one-half of the mice in the fungal burden arm and in one-fourth of the mice in the survival arm, 20 days after the final dose. These data support a loading dose-maintenance dose strategy for quickly reaching highly efficacious VT-1129 concentrations for treating cryptococcal meningitis.

A prospective randomized trial comparing the recovery of platelet function after loading dose administration of prasugrel or clopidogrel

Platelets ◽  
2012 ◽  
Vol 24 (1) ◽  
pp. 15-25 ◽  
Author(s):  
Isabell Bernlochner ◽  
Tanja Morath ◽  
Patricia B. Brown ◽  
Chunmei Zhou ◽  
Brian A. Baker ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Platelet Function ◽  
Prospective Randomized Trial ◽  
Loading Dose ◽  
Dose Administration

scholarly journals The Effect of Ranibizumab Loading Treatment on Vision-Related Quality of Life in Diabetic Macular Edema

2021 ◽  
Vol 11 (3) ◽  
pp. 659-670
Author(s):  
Hatice Daldal ◽  
Mustafa Turkyilmaz ◽  
Melike Balikoglu Yilmaz ◽  
Ufuk Berberoglu
Keyword(s):  
Quality Of Life ◽  
Macular Edema ◽  
Intravitreal Injection ◽  
Diabetic Macular Edema ◽  
Macular Thickness ◽  
Loading Dose ◽  
The Third ◽  
Related Quality ◽  
Composite Scores

Aims: To investigate the changes in vision-related quality of life after a loading dose of three consecutive intravitreal ranibizumab (IVR) injections in patients with unilateral diabetic macular edema (DME). Materials and Methods: Fifty-two eyes of 52 patients who received IVR injections in only one eye with DME were included in our study. The following characteristics of the patients were recorded: gender, education status, marital status, work status, presence of chronic disease. The changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) were evaluated at baseline (before treatment) and 1 month after the third intravitreal injection (after treatment). Patients were administered the Turkish form of the National Eye Institute 25-Item Visual Functions Questionnaire (NEI VFQ-25 TR). The quality of life scores assessed by the NEI VFQ-25 TR, the BCVA, intraocular pressure (IOP), and CMT measurements were compared at baseline (before treatment) and 1 month after the third intravitreal injection (after treatment). Results: We enrolled 52 patients (25 females, 27 males) in our study; mean age was 64.35 ± 9.26 years. After treatment, BCVA improved significantly (p = 0.001), and macular thickness decreased significantly (p < 0.001). All NEI VFQ-25 TR subscale scores were significantly higher after treatment (p < 0.05). However, no significant correlation was found between the change in BCVA and CMT and the change in NEI VFQ-25 TR subscale and composite scores. The increase in near activities scores was significantly higher in males (p = 0.020) and in the retired group (p = 0.022). There were no significant differences in the changes in NEI VFQ-25 TR subscale and composite scores in relation to educational status. Discussion: Significant improvements in BCVA, macular edema, and vision-related quality of life were found in DME patients who received IVR injections with a loading dose, as shown by the NEI VFQ-25 TR. Interestingly, a significant improvement in quality of life was observed even though the patients could see well with the fellow eye. In conclusion, the NEI VFQ-25 TR is a useful scale to evaluate the changes in visual function and psychosocial characteristics of DME patients after treatment.

Effect of sweet almond suspension as anti-inflammatory in experimental infected mice with arthritis

2012 ◽  
Vol 36 (2) ◽  
pp. 98-105
Author(s):  
Lubna A. Kafi
Keyword(s):  
Knee Joint ◽  
Oral Treatment ◽  
Positive Control ◽  
Negative Control ◽  
Histopathological Study ◽  
Histopathological Changes ◽  
The Third ◽  
Incomplete Freund’S Adjuvant ◽  
Test Level ◽  
Sweet Almond

The current study was conduct to determine the effects of oral treatment of sweet Almond Suspension (SAS) on induced arthritis by Incomplete Freund’s Adjuvant (IFA).Seventy mice, with close age and weight were used; they were equally divided in to 7 groups (10 mice per group). The first group served as negative control (non infected – non treated (NINTC). The second group was the positive control (infected non treated, (NINTC) the third and fourth groups were those treated with 1.42 or 2.84 g/kg of SAS respectively. The fifth group was treated with voltarin (ITV), while the sixth and seventh groups were treated with the same closes of SAS but before infection (Prophylactic infected groups, PI1, PI2).The size of knee joint, carrageenan test, level of alkaline phosphatase and histopathological changes in the knee joint used as parameters to compare between groups. The results showed that SAS was able to subside signs of arthritis by decreasing the size of knee and decrease the formation of edema which was induced by injection of carrageenan in the paw of the animal, Histopathological study showed that joints of treated groups by SAS had no signs of arthritis. However, there was slight infiltration of netrophile in treatment and prophylactic group.

Effects of oral administration of ticagrelor on the plasma level of adrenaline, histamine, serotonin, and acetylcholine in rat

2020 ◽  
Author(s):  
Xiuling Yang ◽  
Xue Guo ◽  
Li Yanan ◽  
Li Jiaxi ◽  
Liu Yue
Keyword(s):  
Acute Coronary Syndrome ◽  
Plasma Concentration ◽  
Plasma Level ◽  
Adverse Reactions ◽  
Statistical Significance ◽  
Loading Dose ◽  
Time Points ◽  
Coronary Syndrome ◽  
P2y12 Receptor Antagonist ◽  
First Time

Abstract Background: Ticagrelor as a reversible P2Y12 receptor antagonist which plays an important role in the treatment of acute coronary syndrome (ACS). Dyspnea is one of the main adverse reactions of ticagrelor, however the mechanism is not clearly now. The aim of this study was to assess the possible relationship between ticagrelor-related dyspnea and some neurotransmitter in plasma which can contract the bronchial smooth muscle.Methods: The effects of ticagrelor on the plasma level of adrenaline, histamine, serotonin, and acetylcholine was studied in rats. Ticagrelor was administered at a loading dose of 24 mg/kg for the first time, and then maintenance dose 12 mg/kg, twice a day for 6 days. The plasma level of adrenaline, histamine, serotonin, and acetylcholine was determined by LC-MS/MS.Results: The plasma level of serotonin increased after ticagrelor administrating, especially at 1.5h ( p <0.05) reach the level of statistical significance. The level of serotonin in plasma was consistent with ticagrelor blood concentration. Meanwhile, ticagrelor can cause a decrease in the plasma concentration of histamine, and the change was statistically significant at time points of 1.5h, 3.5h and 10.5h respectively. The concentration of the adrenaline and acetylcholine had no change.Conclusions: The results of this study reveal that ticagrelor can increases blood serotonin levels and this may be a cause of dyspnea ticagrelor-related.

In Vivo Inhibition Of Thromboxane A2-Synthetase : Protective Effect Against Collagen And Arachidonate Infusion

1981 ◽  
Author(s):  
D Sincholle ◽  
C Fontaine ◽  
B Martin ◽  
C Bonne ◽  
P Regnault
Keyword(s):  
Blood Pressure ◽  
Plasma Level ◽  
Oral Treatment ◽  
Lethal Dose ◽  
Thromboxane A2 ◽  
Pharmacokinetic Studies ◽  
Antithrombotic Drugs ◽  
Thromboxane Synthetase ◽  
Derivatives Of

Rabbits and rats anaesthetised with thiopental were infused intravenously either with sodium arachidonate or collagen. Blood pressure and pneumogram were recorded and Thromboxane B2 (T×B2) plasma level was measured prior and after infusion. The aggregating agents elicited hypotension, respiratory break down and killed the animals. These events were associated with an increase in plasma T×B2 concentration. Intraperitoneal pretreatment of animals with derivatives of imidazole (1 -(3-hydroxy-1-oct enyl)-imidazole , chlorhydrat e (CBS6l2) and its nicotinic ester (CBS634) delayed toxic effects and death. In the standard conditions used in this study, the lethal dose of arachidonate in the rabbit was 8.4 t 1.0 mg/kg. This dose was increased to 21.6 ± 4.3 and 50.4 ± 8.0 when the animals were pretreated with CBS6l2 at the dose of respectively 12.5 mg/kg and 25 mg/kg. In the same way, the lethal dose of collagen in the rat was 0.5 ± 0.1 mg/kg in controls and 1.2 t 0.1 mg/kg after treatment with thromboxane-synthetase inhibitor (CBS634 = 25 mg/kg). The lethal dose of collagen was correlated to the concentration of T×B2 formed in the blood (controls : 4.4 ± 0.3 ; treated : 1.7 ± 0.2 ng/ml).Potential interest of these antithrombotic drugs could be strengthened by further pharmacokinetic studies after oral treatment actually in progress.

Clinical and pharmacologic analysis of hyperfractionated daily oral etoposide.

1995 ◽  
Vol 13 (1) ◽  
pp. 191-199 ◽  
Author(s):  
H Minami ◽  
Y Ando ◽  
S Sakai ◽  
K Shimokata
Keyword(s):  
Plasma Level ◽  
Blood Level ◽  
Combination Chemotherapy ◽  
Pharmacokinetic Model ◽  
Oral Etoposide ◽  
Predictive Error ◽  
Major Toxicity ◽  
The Mean ◽  
Stable Plasma ◽  
Pharmacologic Analysis

PURPOSE The antitumor effect of etoposide is increased by maintaining a low blood level, whereas high peak levels may cause myelotoxicity. We investigated whether a constant low blood level could be obtained by the administration of oral etoposide three times daily. PATIENTS AND METHODS Nineteen patients with non-small-cell lung cancer were treated with oral etoposide (25 mg three times daily for 21 days) as monotherapy or in combination with cisplatin 80 mg/m2. A pharmacokinetic model that predicted the mean blood concentration (Cmean) was developed in the 10 patients on etoposide monotherapy and validated in the nine patients on combination chemotherapy. Pharmacodynamic relationships were evaluated in each group. RESULTS Etoposide dose per body-surface area ranged from 45 to 63 mg/m2/d (median, 53), but did not correlate with plasma level. Cmean was 1.1 +/- 0.3 micrograms/mL. Peak concentrations ranged from 0.6 to 2.5 micrograms/mL. The intrapatient coefficient of variation for plasma etoposide concentrations was 22% +/- 10%. Cmean was accurately estimated as follows: Cmean = 0.098 + 0.413 x C0 + 0.458 x C2 (r = .97, P = .0001), where C0 and C2 represent concentrations before and 2 hours after administration. This model was unbiased (mean predictive error [MPE], 0.0 microgram/mL) and precise (root mean square error [RMSE], 0.1 microgram/mL). Leukopenia was the major toxicity. The surviving fraction of leukocytes (SF; nadir count/pretreatment count) was correlated to Cmean as follows: SF = 0.87 - 0.34 x Cmean (r = .67, P = .03) in the monotherapy group and SF = 0.64 - 0.33 x Cmean (R = .77, P = .03) in the combination chemotherapy group. Two and four patients treated with monotherapy and combination chemotherapy showed responses, respectively. All responders had a Cmean > or = 1.0 microgram/mL. CONCLUSION Hyperfractionated oral etoposide achieveda stable plasma level that could be predicted by measurement at only two times.

scholarly journals Plasma levels of cortisol and opioid peptide beta-endorphin during spontaneous vaginal delivery

2006 ◽  
Vol 134 (3-4) ◽  
pp. 95-99
Author(s):  
Ljubica Arsenijevic ◽  
Zvezdana Kojic ◽  
Nada Popovic ◽  
Ljiljana Scepanovic
Keyword(s):  
Plasma Level ◽  
Pregnant Women ◽  
Plasma Levels ◽  
Opioid Peptide ◽  
Labor Pain ◽  
The Third ◽  
Group 3 ◽  
Group 2 ◽  
Underlying Mechanisms ◽  
Group 1

INTRODUCTION Labor pain is very frequent in clinical practice, but the underlying mechanisms as well as numerous neuroendocrine responses activated by such pain have not been fully explained yet. OBJECTIVE The objective of the study was to determine the influence of labor pain on plasma levels of cortisol and opioid peptide ?-endorphin. METHOD Cortisol and ?-endorphin levels were measured in blood plasma of: health, non-pregnant women (group 1, n=8), health pregnant women (group 2, n=8) and in parturitions, through fourth ages (group 3, n=8), Plasma level of cortisol was measured by radioimmunoassay, and ?-endorphin by enzyme immunoassay. Data were expressed as mean ? standard error of mean and were analyzed by Student's t test and Mann Whitney test. RESULTS Plasma level of cortisol in group 2 was significantly increased compared to the group 1. During labor progression, plasma level of cortisol was rising till the third labor age. Plasma level of cortisol in fourth labor age was not significantly different from the ag.e one and group 1. Plasma level of ?-endorphin was (n.g/L): in group 1:64?20, group 2:70?22, group 3:the first labor age: 75?15, the second labor age: 193?54, the third labor age: 346+97 and the fourth labor age: 114?31. CONCLUSION These results indicate that both ?-endorphin and cortisol are involved in regulation and modulation of labor pain and stress.

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