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Bill J Gurley Ashley Swain Gary W Barone D Keith Williams Philip Breen C Ryan Yates Leslie B Stuart Martha A Hubbard Yudong Tong Sreekhar Cheboyina 《Drug metabolism and disposition》2007,35(2):240-245
Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), C(max,) CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC((0-3)), AUC((0-24)), CL/F, t(1/2), and C(max), whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C(max) (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo. 相似文献
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Biologic distribution data in the rat were obtained for the alpha-1 adrenoceptor imaging agent (+/-) 2-[beta-(iodo-4-hydroxyphenyl)ethylaminomethyl]tetralone (HEAT) labeled with [125I]. The major excretory routes were through the liver (67%) and the kidney (33%). Internal radiation absorbed dose estimates to nine source organs, total body, the GI tract, gonads, and red bone marrow were calculated for the human using the physical decay data for [123I]. The critical organ was found to be the lower large intestine, receiving 1.1 rad per mCi of [123I]HEAT administered. The total-body dose was found to be 58 mrad per mCi. 相似文献
35.
The extracellular matrix of stratum corneum: role of lipids in normal and pathological function 总被引:4,自引:0,他引:4
The mammalian stratum corneum, formerly treated as a homogeneous film, is now more properly viewed as a two-compartment system. The cornified cell is protein-enriched and lipid-depleted, lying embedded in an expanded extracellular matrix of highly nonpolar lipids. Because of its strategic location between the cornified layer, this lipid matrix is responsible for many phenomena related to the permeability barrier, as well as cohesion and desquamation. Thus, manipulation of this compartment could lead to enhanced drug delivery and improved lubrication, as well. 相似文献
36.
Peter J. Morgan Lynda M. Williams Gary Davidson Wilfred Lawson Edward Howell 《Journal of neuroendocrinology》1989,1(1):1-4
The functional significance of the pars tuberalis (PT) of the mammalian adenohypophysis has remained an enigma (1, 2). One view of its function is that it acts as an auxiliary gland to support the endocrine role of the pars distalis (PD) (2), as it has been shown to contain immunocytochemically identifiable thyrotrophs and gonadotrophs (1). Many of the cells of the PT are, however, ultrastructurally unique suggesting an independent function for this tissue. Our recent demonstration that the PT of the rat is a major binding site for the ligand iodomelatonin lends further support to this idea (3). We have utilized the highly specific ligand [125 l]melatonin, and have demonstrated that it binds exclusively, with very high affinity, to the PT but not the PD of the adult sheep adenohypophysis. These findings support the conclusion that the PT has a distinct role in relation to melatonin action and seasonal reproduction. 相似文献
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1 The internal anal sphincter (IAS) has a spontaneous tone and is the main contributor to the maintenance of faecal continence. The spontaneous resting tone exhibited by the sphincter can be modified by neurotransmitters from the autonomic and enteric nervous systems. 2 In this review, the influence of the sympathetic and parasympathetic nervous systems on IAS tone are discussed and the putative roles of nitric oxide, carbon monoxide, vasoactive intestinal peptide and adenosine triphosphate in non‐adrenergic non‐cholinergic transmission are considered. 3 Faecal incontinence is a common condition that places a heavy financial burden on the health service and severely affects patients’ quality of life. Resting anal pressure is reduced in patients with faecal incontinence and agents that increase sphincter tone tend to relieve symptoms. The results of clinical studies of the use of phenylephrine to treat faecal incontinence are reviewed. 4 It is concluded that the IAS is a potential target for drug development for the treatment of faecal incontinence. 相似文献
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Pain management in ambulatory surgery. 总被引:1,自引:0,他引:1
Damon Kamming Frances Chung Donna Williams Brid M McGrath Bruna Curti 《Journal of PeriAnesthesia Nursing》2004,19(3):174-182
Successful ambulatory surgery is dependent on analgesia that is effective, has minimal adverse effects, and can be safely managed by the patient at home after discharge. A number of studies have identified that the provision of effective postoperative analgesia is inadequate for a significant proportion of patients. The following discussion details the current available analgesic options for ambulatory surgery patients and the rationale for their use. Preemptive analgesia should be given to all patients unless there are specific contraindications. Consideration should be given to the use of long-acting oral COX-2 selective nonsteroidal anti-inflammatory drugs (NSAIDs) and long-acting oral opioids to treat postoperative pain. A standardized multimodal postdischarge analgesic regimen tailored to the patient's expected postoperative pain levels should be prescribed. Patient follow-up by telephone questionnaire will confirm those surgical procedures that result in mild or moderate-to-severe postoperative pain and the effectiveness of treatment plans. 相似文献