Evaluation of Zingiber officinale Effects on Rifampicin Pharmacokinetic Parameters Using Animal Model

1988 ◽  
Vol 158 (4) ◽  
pp. 831-847 ◽  
Author(s):  
B. Vogelman ◽  
S. Gudmundsson ◽  
J. Leggett ◽  
J. Turnidge ◽  
S. Ebert ◽  
...  

2006 ◽  
Vol 34 (05) ◽  
pp. 845-855 ◽  
Author(s):  
Hsiu-Mei Chiang ◽  
Pei-Dawn Lee Chao ◽  
Su-Lan Hsiu ◽  
Kuo-Ching Wen ◽  
Shang-Yuan Tsai ◽  
...  

Ginger (roots of Zingiber officinale ROSCOE) is a popular spice and herbal medicine worldwide. Cyclosporine is clinically used as an important immunosupressant with narrow therapeutic index. This study attempted to investigate the effect of ginger juice on the pharmacokinetics of cyclosporine in rats. Rats were orally administered cyclosporine alone and in combination with ginger juice (5 ml/kg) concomitantly, as well as 2 hours after the ginger juice, respectively, in crossover designs. In addition, rats were intravenously administered cyclosporine with and without an oral dose of ginger juice (5 ml/kg). The blood samples were withdrawn via cardiopuncture at determined time points and cyclosporine concentrations were determined by a specific monoclonal fluorescence polarization immunoassay. The pharmacokinetic parameters of cyclosporine were calculated using a non-compartment model of WINNONLIN. The results indicated that concomitant intake of ginger significantly decreased Cmaxand AUC0–tof oral cyclosporine by 70.9% and 63.1%, respectively. The intake of ginger 2 hours before cyclosporine significantly decreased Cmaxand AUC0–tby 51.4% and 40.3%, respectively. In contrast, the pharmacokinetics of intravenous cyclosporine not altered by orally in combination with ginger juice. In conclusion, ginger significantly decreased the oral bioavailability of cyclosporine, and the interaction should occur at the absorption phase. Patients treated with cyclosporine should be discouraged from using ginger products to ensure the efficacy of cyclosporine.


ADMET & DMPK ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 279-283
Author(s):  
Seth Kwabena Amponsah ◽  
Kwabena Frimpong-Manso Opuni ◽  
Ama Asiedua Donkor

Corticosteroids, such as betamethasone, are sometimes administered to women who are at risk of pre-term delivery. These corticosteroids cross the placenta to the fetus and decrease respiratory distress syndrome in preterm newborns. Preterm newborns are often susceptible to infections partly due to their immature immune system. Amikacin is one of the aminoglycosides used in the treatment of newborn infections. There is, however, a dearth of information on the effect of prenatal corticosteroids on the disposition of aminoglycosides administered to newborns days later. We evaluated the effect of pre-administration of betamethasone on the disposition of amikacin, 72 h after last dose of betamethasone, using an animal model. The pharmacokinetic parameters of rats administered betamethasone followed by amikacin vis-a-vis rats administered saline followed by amikacin were as follows: Cmax; 16.6 μmol L-1 vs. 31.4 μmol L-1, AUC0→8; 26.8 μmol h L-1 vs. 153.5 μmol h L-1, Ke; 0.26 h-1 vs. 0.18 h-1, and t1/2; 2.6 h vs. 3.9 h, respectively. About a 1.5-fold increase in the elimination of amikacin was observed in the Sprague-Dawley rats pre-treated with betamethasone compared with those pre-treated with saline. This ultimately led to differences in the other pharmacokinetic parameters amongst the two groups of rats. Although an animal model investigation showed some level of interaction, a follow-up study in preterm newborns where possible interaction of the two drugs is studied later than Day 1, is recommended.


1996 ◽  
Vol 40 (3) ◽  
pp. 642-645 ◽  
Author(s):  
P Rajagopalan ◽  
F D Boudinot ◽  
C K Chu ◽  
B C Tennant ◽  
B H Baldwin ◽  
...  

The woodchuck (Marmota monax) has proven to be a suitable animal model for studying hepatitis B virus (HBV) infection owing to similarities in the course of infection between woodchuck hepatitis virus (WHV) in woodchucks and HBV in humans. (-)-beta-L-2',3'-Dideoxy-3'-thiacytidine (3TC; lamivudine) is a nucleoside analog which has demonstrated antiviral activity against HBV as well as human immunodeficiency virus (HIV). The purpose of the present investigation was to characterize the pharmacokinetics of 3TC following intravenous and oral administration of 20 mg of 3TC per kg of body weight to woodchucks. Following intravenous administration, the concentrations of 3TC in plasma declined, with a terminal half-life of 2.84 +/- 0.85 h (mean +/- standard deviation). The systemic clearance and steady-state volume of distribution of 3TC were 0.22 +/- 0.078 liters/h/kg and 0.75 +/- 0.13 liters/kg, respectively. The renal clearance of the nucleoside analog was 0.063 +/- 0.016 liters/h/kg. The oral bioavailability of 3TC ranged from 18 to 54%. Allometric relationships between pharmacokinetic parameters and body weight developed by Hussey et al. (E.K. Hussey, K.H. Donn, M.J. Daniel, S.T. Hall, A.J. Harker, and G.L. Evans, J. Clin. Pharmacol. 34:975-977, 1994) were augmented by including data from woodchucks, monkeys (S.M. Blaney, M.J. Daniel, A.J. Harker, K. Godwin, and F.M. Balis, Antimicrob. Agents Chemother. 39:2779-2782, 1995), and additional data from rats (P. Rajagopalan, L. Moore, C.K. Chu, R.F. Schinazi, and F.D. Boudinot, submitted for publication). Interspecies scaling of the pharmacokinetic parameters of 3TC demonstrated a good correlation between clearance (0.74 . W0.76 [where W is body weight]; r = 0.93; P < 0.025), apparent volume of distribution (1.62 . W0.81; r = 0.98; P < 0.005), and steady-state volume of distribution (1.09 . W0.94; r = 0.99; P < 0.05) and species body weight. The allometric relationships for clearance and volume of distribution at steady state predicted the observed pharmacokinetic parameters in humans quite well; however, the apparent volume of distribution was underestimated in humans. Thus, the pharmacokinetic data obtained with the woodchuck HBV animal model should be useful for designing clinical trials.


Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs

Gonadotroph cell adenomas of the pituitary are infrequent in human patients and are not invariably associated with altered gonadal function. To date, no animal model of this tumor type exists. Herein, we describe spontaneous gonadotroph cell adenomas in old male and female Sprague-Dawley rats by histology, immunocytology and electron microscopy.The material consisted of the pituitaries of 27 male and 38 female Sprague Dawley rats, all 26 months of age or older, removed at routine autopsy. Sections of formal in-fixed, paraffin-embedded tissue were stained with hematoxylin-phloxine-saffron (HPS), the PAS method and the Gordon-Sweet technique for the demonstration of reticulin fibers. For immunostaining, sections were exposed to anti-rat β-LH, anti-ratβ-TSH, anti-rat PRL, anti-rat GH and anti-rat ACTH 1-39. For electron microscopy, tissue was fixed in 2.5% glutaraldehyde, postfixed in 1% OsO4 and embedded in epoxy-resin. Tissue fixed in 10% formalin, embedded in epoxy resin without osmification, was used for immunoelectron microscopy.


Author(s):  
G. C. Smith ◽  
R. L. Heberling ◽  
S. S. Kalter

A number of viral agents are recognized as and suspected of causing the clinical condition “gastroenteritis.” In our attempts to establish an animal model for studies of this entity, we have been examining the nonhuman primate to ascertain what viruses may be found in the intestinal tract of “normal” animals as well as animals with diarrhea. Several virus types including coronavirus, adenovirus, herpesvirus, and picornavirus (Table I) were detected in our colony; however, rotavirus, astrovirus, and calicivirus have not yet been observed. Fecal specimens were prepared for electron microscopy by procedures reported previously.


Author(s):  
J. Metuzals

It has been demonstrated that the neurofibrillary tangles in biopsies of Alzheimer patients, composed of typical paired helical filaments (PHF), consist also of typical neurofilaments (NF) and 15nm wide filaments. Close structural relationships, and even continuity between NF and PHF, have been observed. In this paper, such relationships are investigated from the standpoint that the PHF are formed through posttranslational modifications of NF. To investigate the validity of the posttranslational modification hypothesis of PHF formation, we have identified in thin sections from frontal lobe biopsies of Alzheimer patients all existing conformations of NF and PHF and ordered these conformations in a hypothetical sequence. However, only experiments with animal model preparations will prove or disprove the validity of the interpretations of static structural observations made on patients. For this purpose, the results of in vitro experiments with the squid giant axon preparations are compared with those obtained from human patients. This approach is essential in discovering etiological factors of Alzheimer's disease and its early diagnosis.


Author(s):  
V.J. Montpetit ◽  
S. Dancea ◽  
L. Tryphonas ◽  
D.F. Clapin

Very large doses of pyridoxine (vitamin B6) are neurotoxic in humans, selectively affecting the peripheral sensory nerves. We have undertaken a study of the morphological and biochemical aspects of pyridoxine neurotoxicity in an animal model system. Early morphological changes in dorsal root ganglia (DRG) associated with pyridoxine megadoses include proliferation of neurofilaments, ribosomes, rough endoplasmic reticulum, and Golgi complexes. We present in this report evidence of the formation of unique aggregates of microtubules and membranes in the proximal processes of DRG which are induced by high levels of pyridoxine.


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