Prednisolone and dexamethasone are systemically absorbed after topical application of ophthalmic suspensions in healthy dogs

2022 ◽  
pp. 1-10
Author(s):  
Margaret M. Ewald ◽  
Amy J. Rankin ◽  
Jessica M. Meekins ◽  
Geraldine Magnin ◽  
Butch KuKanich
Keyword(s):  
Plasma Cortisol ◽  
Healthy Adult ◽  
Plasma Concentrations ◽  
Polymyxin B ◽  
Systemic Absorption ◽  
Prednisolone Acetate ◽  
Drug Concentrations ◽  
Ophthalmic Administration ◽  
Median Plasma ◽  
Healthy Dogs

Abstract OBJECTIVE To quantify plasma concentrations of prednisolone and dexamethasone (peripheral and jugular) and cortisol following topical ophthalmic application of 1% prednisolone acetate and 0.1% dexamethasone to healthy adult dogs. ANIMALS 12 purpose-bred Beagles. PROCEDURES Dogs received 1 drop of 1% prednisolone acetate (n = 6) or neomycin polymyxin B dexamethasone (ie, 0.1% dexamethasone; 6) ophthalmic suspension in both eyes every 6 hours for 14 days. Blood samples (peripheral and jugular) were collected on days 0, 1, 7, and 14 and analyzed for plasma prednisolone and dexamethasone concentrations. Plasma cortisol concentrations were measured at the beginning of the study and following topical drug administration. RESULTS Both drugs demonstrated systemic absorption. Prednisolone was detected on days 1, 7, and 14 (median plasma concentration, 24.80 ng/mL; range, 6.20 to 74.00 ng/mL), and dexamethasone was detected on days 1, 7, and 14 (2.30 ng/mL; 0 to 17.70 ng/mL). Neither prednisolone nor dexamethasone were detected in plasma samples on day 0 (baseline). Sampling from the jugular vein resulted in higher plasma drug concentrations than from a peripheral vein when samples from each day were combined. Plasma cortisol concentrations were significantly lower than baseline following 14 days of treatment with topical prednisolone acetate and dexamethasone. CLINICAL RELEVANCE Prednisolone and dexamethasone are detected in the plasma of healthy dogs following topical ophthalmic administration 4 times/d with prednisolone concentrations being close to a physiologic dose of orally administered prednisolone. Additional research is needed to evaluate the systemic absorption of these medications in dogs with ocular inflammation.

scholarly journals Comparison of Plasma, Epithelial Lining Fluid, and Alveolar Macrophage Concentrations of Solithromycin (CEM-101) in Healthy Adult Subjects

2012 ◽  
Vol 56 (10) ◽  
pp. 5076-5081 ◽  
Author(s):  
Keith A. Rodvold ◽  
Mark H. Gotfried ◽  
J. Gordon Still ◽  
Kay Clark ◽  
Prabhavathi Fernandes
Keyword(s):  
Steady State ◽  
High Performance ◽  
Healthy Adult ◽  
Plasma Concentrations ◽  
Epithelial Lining ◽  
Time Curve ◽  
Epithelial Lining Fluid ◽  
Once Daily ◽  
Drug Concentrations ◽  
The Mean

ABSTRACTThe steady-state concentrations of solithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained from intrapulmonary samples during bronchoscopy and bronchoalveolar lavage (BAL) in 30 healthy adult subjects. Subjects received oral solithromycin at 400 mg once daily for five consecutive days. Bronchoscopy and BAL were carried out once in each subject at either 3, 6, 9, 12, or 24 h after the last administered dose of solithromycin. Drug concentrations in plasma, ELF, and AM were assayed by a high-performance liquid chromatography-tandem mass spectrometry method. Solithromycin was concentrated extensively in ELF (range of mean [± standard deviation] concentrations, 1.02 ± 0.83 to 7.58 ± 6.69 mg/liter) and AM (25.9 ± 20.3 to 101.7 ± 52.6 mg/liter) in comparison with simultaneous plasma concentrations (0.086 ± 0.070 to 0.730 ± 0.692 mg/liter). The values for the area under the concentration-time curve from 0 to 24 h (AUC0–24values) based on mean and median ELF concentrations were 80.3 and 63.2 mg · h/liter, respectively. The ratio of ELF to plasma concentrations based on the mean and median AUC0–24values were 10.3 and 10.0, respectively. The AUC0–24values based on mean and median concentrations in AM were 1,498 and 1,282 mg · h/L, respectively. The ratio of AM to plasma concentrations based on the mean and median AUC0–24values were 193 and 202, respectively. Once-daily oral dosing of solithromycin at 400 mg produced steady-state concentrations that were significantly (P< 0.05) higher in ELF (2.4 to 28.6 times) and AM (44 to 515 times) than simultaneous plasma concentrations throughout the 24-h period after 5 days of solithromycin administration.

scholarly journals Comparison of Intrathecal Concentrations of Acyclovir following Epidural and Intravenous Administration in Rats

2016 ◽  
Vol 4;19 (4;5) ◽  
pp. E613-E619
Author(s):  
Sang Sik Choi
Keyword(s):  
Herpes Zoster ◽  
Varicella Zoster Virus ◽  
Plasma Concentrations ◽  
Cranial Nerves ◽  
Group Iv ◽  
Epidural Administration ◽  
Varicella Zoster ◽  
Drug Concentrations ◽  
Median Plasma ◽  
Intrathecal Space

Background: Herpes zoster is a disease caused by reactivation of varicella-zoster virus in sensory cranial nerves and dorsal root ganglion. Our presumption was that epidural administration of acyclovir near the viral burden could be more advantageous than intravenous (IV) administration. The cerebrospinal fluid (CSF) concentration of acyclovir after epidural administration was determined to be higher than that after IV administration in rats. Objective: In this study, we tested the hypothesis that the concentration of acyclovir in CSF after epidural administration is higher than that achieved after IV administration in rats. Study Design: A randomized controlled animal trial. Methods: A total of 30 adult male Sprague-Dawley rats were used. The rats were randomly divided into 2 equal groups, epidural (Group Epi) and IV (Group IV) administration groups (n = 15). Group Epi was further subdivided into 3 groups according to acyclovir dosage; each group comprised 5 animals receiving injections at dosages of 0.3 mg, 0.6 mg, and 0.9 mg. Group IV was also subdivided into 3 groups receiving dosages of 3 mg, 6 mg, and 9 mg. We measured CSF and plasma acyclovir concentrations one hour after administration. Results: In Group Epi, the median plasma concentrations of acyclovir were lower than that in CSF (P < 0.05). In Group IV, the median plasma concentrations of acyclovir were significantly higher than that in CSF (P < 0.05). The CSF concentrations of acyclovir in Group Epi were significantly higher than that in Group IV (P < 0.05). The plasma concentrations of acyclovir in Group Epi were significantly lower than that in Group IV (P < 0.05). Limitations: There were no references of equivalent dosages of acyclovir between IV and epidural administration. However, it is obvious in this study that epidural administration of a low dose of acyclovir can more effectively increase its concentration in the intrathecal space than IV administration. Conclusions: Epidural administration of acyclovir provides superior drug concentrations in the intrathecal space compared to IV administration. Key words: Acyclovir, epidural injection, herpes zoster, varicella zoster virus

Activated Charcoal in Tricyclic Antidepressant Poisoning

1988 ◽  
Vol 7 (4) ◽  
pp. 307-310 ◽  
Author(s):  
B-Å. Hultén ◽  
R. Adams ◽  
R. Askenasi ◽  
V. Dallos ◽  
S. Dawling ◽  
...  
Keyword(s):  
Single Dose ◽  
Activated Charcoal ◽  
Peak Plasma ◽  
Randomized Study ◽  
Plasma Concentrations ◽  
Gastric Lavage ◽  
Systemic Absorption ◽  
Plasma Drug ◽  
Drug Concentrations ◽  
Significant Difference

Tricyclic antidepressants (TCA) bind to activated charcoal both in vitro and in vivo in healthy volunteers after a therapeutic dose of TCA. These findings provide a basis for the routine use of activated charcoal in TCA poisoning. The object of this study was to examine the effect of a single dose of 20 g of activated charcoal in overdose patients. Ninety-one patients from four centres with suspected TCA overdose were entered into a randomized study. Gastric lavage was performed on all patients. Thirty-four received 20 g of activated charcoal and 43 served as controls. Fourteen patients were excluded. Plasma drug concentrations were taken on admission and at 1, 2, 4, 8 and 24 h. The incidence of toxic symptoms was registered during 24 h. There was no significant difference in the area under the plasma drug concentration versus time curve, the peak plasma concentrations or plasma half-lives between the two groups. Toxic symptoms were more frequent in the non-treated groups although this difference was not statistically significant. In patients with TCA overdose initially treated with gastric lavage, a single dose of 20 g of activated charcoal had no effect on the systemic absorption or elimination of TCA.

Elevated Circulating P-Selectin in Insulin Dependent Diabetes Mellitus

1996 ◽  
Vol 76 (03) ◽  
pp. 328-332 ◽  
Author(s):  
Bernd Jilma ◽  
Peter Fasching ◽  
Christine Ruthner ◽  
Anna Rumplmayr ◽  
Sabine Ruzicka ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Insulin Dependent Diabetes Mellitus ◽  
Interquartile Range ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Intergroup Comparison ◽  
Median Plasma ◽  
Insulin Dependent

SummaryBased on findings that showed increased P-selectin expression on platelets and on choroidal microvessels of patients with insulin dependent diabetes mellitus (IDDM), we hypothesized that also plasma concentrations of circulating (c)P-selectin would be increased in these patients.The aim of this study was to compare the plasma levels of cP-selec-tin between non-smoking patients with IDDM, treated with an intensified insulin therapy, and healthy controls. The study design was prospective, cross-sectional and analyst-blinded. Subjects were matched individually for sex, age and body mass index. Plasma levels of cP-selectin and of von Willebrand antigen (vWF-Ag) were determined by enzyme linked immunoassays.Forty-two pairs were available for intergroup comparison. Median plasma concentrations of cP-selectin in patients with IDDM (285 ng/ml; interquartile range: 233-372) were on average 21% higher than those of controls (236 ng/ml; interquartile range: 175-296; p = 0.004). Also, median plasma levels of vWF-Ag were 10% higher in patients (96 U/dl; interquartile range: 82-127) than controls (87 U/dl; interquartile range: 70-104; p = 0.025). There was no correlation between plasma concentrations of cP-selectin and vWF-Ag levels in either group (p ώ0.05).In conclusion, our results of increased cP-selectin levels are in line with increased P-selectin expression on platelets and on choroidal microvessels found in patients with IDDM. In view of the currently developed small molecule inhibitors of cell adhesion molecules, these independent observations together may provide a sound rationale to select P-selectin as a target for treating or preventing IDDM-associated micro- or macrovascular complications.

EARLY VARIATIONS OF PLASMA CORTISOL AFTER PULSE INTRAVENOUS INJECTION OF DIBUTYRYL CYCLIC ADENOSINE 3′,5′-MONOPHOSPHATE IN NORMAL SUBJECTS

1973 ◽  
Vol 72 (4) ◽  
pp. 753-761 ◽  
Author(s):  
Alberto Angeli ◽  
Giuseppe Boccuzzi ◽  
Roberto Frajria ◽  
Daniela Bisbocci ◽  
Franco Ceresa
Keyword(s):  
Intravenous Injection ◽  
Plasma Cortisol ◽  
Time Course ◽  
Healthy Adult ◽  
Normal Subjects ◽  
Adult Women ◽  
Healthy Women ◽  
Adrenal Steroidogenesis ◽  
The Mean ◽  
Zero Time

ABSTRACT 10 mg/kg of dibutyryl cyclic adenosine 3′,5′-monophosphate (Db-cAMP) was iv pulse injected into twelve healthy adult women. The plasma cortisol levels were determined as 11-OHCS at zero time and then at 2.5, 5, 7.5, 10, 15, 30, 60 and 180 min after the injection. The data were compared with those obtained at the corresponding times in two groups of eleven and seventeen healthy women after the injection of 250 ng and 250 μg of synthetic β-1-24 corticotrophin performed in the same manner as the injection of the nucleotide. The mean increments in plasma cortisol were significantly lower after Db-cAMP than after ACTH. Differences were noted by analyzing the time course of the responses. In the case of stimulation with Db-cAMP the 11-OHCS levels rose progressively to a maximum at 15–30 min. By contrast, a peak of plasma cortisol was evident in most cases within a few min after the injection of ACTH; after a fall, a later rise was then observed starting from 15 min. The differences in the plasma 11-OHCS responses after the two stimuli may also be of interest clinically for the investigation of some aspects of adrenal steroidogenesis.

Clinical Impact of Co-medication of Levetiracetam and Clobazam with Proton Pump Inhibitors: A Drug Interaction Study

2020 ◽  
Vol 21 (2) ◽  
pp. 126-131
Author(s):  
Bhuvanachandra Pasupuleti ◽  
Vamshikrishna Gone ◽  
Ravali Baddam ◽  
Raj Kumar Venisetty ◽  
Om Prakash Prasad
Keyword(s):  
Plasma Concentration ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Plasma Concentrations ◽  
Control Group ◽  
Drug Concentrations ◽  
Significant Difference ◽  
Post Hoc ◽  
Hydrolysis Of ◽  
Cytochrome P 450

Background: Clobazam (CLBZ) metabolized primarily by Cytochrome P-450 isoenzyme CYP3A4 than with CYP2C19, Whereas Levetiracetam (LEV) is metabolized by hydrolysis of the acetamide group. Few CYP enzymes are inhibited by Proton Pump Inhibitors (PPIs) Pantoprazole, Esomeprazole, and Rabeprazole in different extents that could affect drug concentrations in blood. The aim of the present study was to evaluate the effect of these PPIs on the plasma concentrations of LEV and CLBZ. Methods: Blood samples from 542 patients were included out of which 343 were male and 199 were female patients and were categorized as control and test. Plasma samples analyzed using an HPLC-UV method. Plasma concentrations were measured and compared to those treated and those not treated with PPIs. One way ANOVA and games Howell post hoc test used by SPSS 20 software. Results: CLBZ concentrations were significantly 10 folds higher in patients treated with Pantoprazole (P=0.000) and 07 folds higher in patients treated with Esmoprazole and Rabeprazole (P=0.00). Whereas plasma concentration of LEV control group has no statistical and significant difference when compared to pantoprazole (P=0.546) and with rabeprazole and esomeprazole was P=0.999. Conclusion: The effect of comedication with PPIs on the plasma concentration of clobazam is more pronounced for pantoprazole to a greater extent when compared to esomeprazole and rabeprazole. When pantoprazole is used in combination with clobazam, dose reduction of clobazam should be considered, or significance of PPIs is seen to avoid adverse effects.

scholarly journals Intranasal administration of the chemotherapeutic perillyl alcohol results in selective delivery to the cerebrospinal fluid in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Geetika Nehra ◽  
Shannon Andrews ◽  
Joan Rettig ◽  
Michael N. Gould ◽  
Jill D. Haag ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Tumors ◽  
Nasal Mucosa ◽  
Brain Cancer ◽  
Intranasal Administration ◽  
High Performance ◽  
Early Stage ◽  
Plasma Concentrations ◽  
Perillyl Alcohol ◽  
Systemic Absorption

AbstractPerillyl alcohol (POH) has been extensively studied for the treatment of peripheral and primary brain tumors. The intranasal route of administration has been preferred for dosing POH in early-stage clinical trials associated with promising outcomes in primary brain cancer. However, it is unclear how intranasal POH targets brain tumors in these patients. Multiple studies indicate that intranasally applied large molecules may enter the brain and cerebrospinal fluid (CSF) through direct olfactory and trigeminal nerve-associated pathways originating in the nasal mucosa that bypass the blood–brain barrier. It is unknown whether POH, a small molecule subject to extensive nasal metabolism and systemic absorption, may also undergo direct transport to brain or CSF from the nasal mucosa. Here, we compared CSF and plasma concentrations of POH and its metabolite, perillic acid (PA), following intranasal or intravascular POH application. Samples were collected over 70 min and assayed by high-performance liquid chromatography. Intranasal administration resulted in tenfold higher CSF-to-plasma ratios for POH and tenfold higher CSF levels for PA compared to equal dose intravascular administration. Our preclinical results demonstrate POH undergoes direct transport from the nasal mucosa to the CSF, a finding with potential significance for its efficacy as an intranasal chemotherapeutic for brain cancer.

Effects of diltiazem on atrioventricular conduction and arterial blood pressure: correlation with plasma drug concentrations

1984 ◽  
Vol 62 (12) ◽  
pp. 1479-1486 ◽  
Author(s):  
Jean-Paul Clozel ◽  
Jacques Billette ◽  
Gilles Caillé ◽  
Pierre Théroux ◽  
Richard Cartier
Keyword(s):  
Blood Pressure ◽  
Plasma Concentration ◽  
Refractory Period ◽  
Plasma Concentrations ◽  
Atrioventricular Conduction ◽  
Gas Liquid Chromatography ◽  
Conduction Time ◽  
Arterial Blood ◽  
Drug Concentrations ◽  
Atrial Conduction Time

Atrial and atrioventricular conduction variables were studied at control and at the end of each of six consecutive 45-min diltiazem administration periods in eight closed chest-anesthetized dogs. Diltiazem was given as a bolus (50 μg/kg, i.v.) followed by an infusion (0.5 μg∙kg−1∙min−1); doses were doubled in subsequent periods. The plasma concentrations, measured by gas–liquid chromatography, ranged from 8 to 1400 ng/mL and correlated strongly with the doses (r = 0.92; p < 0.01). The Wenckebach cycle length, basic conduction time, and functional refractory period of the atrioventricular (AV) node increased proportionally with plasma concentration (respective r = 0.90, 0.89, 0.80; p < 0.01). The minimum mean plasma concentrations affecting these variables significantly were 37, 83, and 175 ng/mL, respectively. Second or third degree AV blocks developed in all dogs for plasma concentrations between 379 and 1400 ng/mL. In four dogs which were given isoproterenol (0.2 μg∙kg−1∙min−1), these blocks disappeared within 1 min. Atrial conduction time and functional refractory period were slightly but significantly shortened by diltiazem with mean plasma concentrations of 175 ng/mL and over. His–Purkinje intervals were not significantly changed by diltiazem. Systolic and diastolic arterial pressures were decreased by diltiazem (r = −0.64, r = −0.79; p < 0.01) starting with a mean plasma concentration of 83 ng/mL. We conclude that AV nodal conduction variables are progressively prolonged with increasing plasma concentrations of diltiazem; plasma concentrations affecting blood pressure and AV nodal variables overlap; and the AV blocks produced by toxic concentrations of diltiazem can be corrected by isoproterenol.

Plasma concentration and uterine and ovarian expressions of insulin-like growth factor-2 in dogs with cystic endometrial hyperplasia–pyometra

2021 ◽  
Author(s):  
Nilgün Gültiken ◽  
Murat Yarim ◽  
Gül Fatma Yarim ◽  
Mahmut Sözmen ◽  
Elvan Anadol ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Growth Factor ◽  
Endometrial Hyperplasia ◽  
Endocrine Cells ◽  
Inflammatory Process ◽  
Plasma Concentrations ◽  
Insulin Like Growth Factor ◽  
Healthy Dogs ◽  
Group 2 ◽  
Group 1

AbstractThe objective of this study was to investigate the plasma concentrations of insulin-like growth factor-2 (IGF-2) as well as its expression in the uterus and ovary of healthy dogs and those with cystic endometrial hyperplasia (CEH)–pyometra complex. Group 1 (n = 10) included bitches with open cervix pyometra, while Group 2 (n = 7) consisted of clinically healthy bitches in dioestrus. The number of IGF-2 immunopositive interstitial cells was significantly higher in Group 1, whereas in Group 2 there were only two cases in which a few cells were IGF-2 immunopositive. IGF-2 immunopositivity was observed in the endometrial glandular epithelium in both groups. Additionally, interstitial fibroblasts and macrophages in the endometrium were also positive in Group 1. The concentration of plasma IGF-2 was higher in Group 1 than in Group 2 (P < 0.05). The concentration was positively correlated with IGF-2 expression in the endometrial glands (r = 0.926; P < 0.001) in Group 1. However, a negative correlation was present between plasma IGF-2 concentration and IGF-2 expression in the interstitial endocrine cells of the ovary in Group 1 (r = −0.652; P < 0.05). The results suggest that IGF-2 plays an important role during the inflammatory process occurring in bitches with CEH–pyometra complex as well as in the endometrium of healthy bitches in dioestrus.

scholarly journals The intravenous pharmacokinetics of diminazene in healthy dogs

2009 ◽  
Vol 80 (4) ◽  
Author(s):  
V. Naidoo ◽  
M.S.G. Mulders ◽  
G.E. Swan
Keyword(s):  
Plasma Concentrations ◽  
Compartmental Analysis ◽  
Central Compartment ◽  
Volume Of Distribution ◽  
Time Profile ◽  
Secondary Peak ◽  
German Shepherd ◽  
Plasma Pharmacokinetics ◽  
Healthy Dogs ◽  
Over 40 Years

Diminazene remains one of South Africa's most commonly used antiprotozoal agents for the management of babesiosis in dogs . Although the drug has been on the market for over 40 years, its intravenous pharmacokinetics are poorly known. To better understand the pharmacokinetics of the drug Berenil®, it was reconstituted in sterile water and administered intravenously to 6 adult German shepherd dogs. All 6 dogs demonstrated the previously described secondary peak in the plasma concentration versus time profile. The plasma pharmacokinetics for diminazene are described by both non-compartmental and compartmental models. From non-compartmental analysis, the area under curve to the last sample point (AUClast), clearance (CL) and volume of distribution (Vz) were 4.65±1.95 ng/mℓ/h, 0.77±0.18 ℓ/kg/h and 2.28±0.60 ℓ/kg, respectively. For compartmental modelling, the plasma concentrations were fitted to both a 2-compartmental open model and a recirculatory enterohepatic model. From the recirculation model, the rate of release and re-entry into the central compartment varied markedly with the rate of release from the gall bladder (Ttom) being estimated at 27 ± 20.90 h. Once released, drug re-entry into the central compartment was variable at 9.70±5.48 h. With normal biliary excretion time being about 2 h, this indicates that the redistribution cannot be occurring physiologically from the bile. Although it was not possible to identify the site from which sequestration and delayed release is occurring, it is believed that it is most likely from the liver. The study therefore showed that the secondary peak described for the pharmacokinetics of intramuscular administered diminazene in the dog is not related to biphasic absorption.

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