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Biomedical subjects

A Tsuchida

Publications and source records attributed to A Tsuchida.

At least 109 records · Page 6Linked to original sources
PubMed1994

alpha 1-adrenergic agonists precondition rabbit ischemic myocardium independent of adenosine by direct activation of protein kinase C.

Ischemic preconditioning in the rabbit is initiated by adenosine A1-receptor stimulation, which activates protein kinase C (PKC). Additionally, alpha 1-adrenergic agonists can similarly protect ischemic myocardium, but there has been confusion about the role adenosine receptors play in this protection. To characterize the interaction between adrenergic and adenosine receptors and to study the possible role of PKC in this protection, we used isolated rabbit hearts perfused with oxygenated Krebs' buffer. All hearts were subjected to 30 minutes of regional myocardial ischemia and 2 hours of reperfusion. Infarct size was determined by triphenyltetrazolium staining. Pharmacologic preconditioning in hearts with a 5-minute phenylephrine (PE) infusion 10 minutes before the prolonged regional ischemia resulted in significantly smaller infarcts (9.7 +/- 1.3% of risk area) than in control hearts (31.0 +/- 2.6%, P < .05). This protection could be effectively blocked by administration of the alpha-adrenergic blocker phenoxybenzamine. Methoxamine, an alpha 1a-selective agonist, failed to protect, whereas the alpha 1b-selective antagonist chloroethylclonidine aborted the protective effect of PE. Polymyxin B, an inhibitor of PKC, also blocked the protective effect of PE, implying that PKC has an important role in preconditioning. The adenosine receptor blocker 8-(p-sulfophenyl)theophylline (SPT) given at the same time as the PE infusion did not affect the protection, implying that an alpha 1-agonist could initiate protection independent of adenosine, presumably by direct coupling to PKC. However, the protective effect of PE could be blocked if SPT were administered during the 30-minute regional ischemia. This observation suggested that adenosine receptor occupancy is necessary during long ischemia to reactivate PKC and mediate the protection. However, the addition of a second PE infusion beginning 5 minutes before and continuing throughout the long ischemic period restored the protective effect of PE despite the presence of SPT. Thus, as long as at least one of the receptors (alpha 1-adrenegic or adenosine A1) is activated during long ischemia, protection will be realized. These data indicate that alpha 1 receptors do not precondition through an adenosine intermediate but that alpha 1-adrenergic and adenosine receptors activate parallel pathways within the myocyte that can trigger and mediate protection.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1994

[A study of various complications in arterial infusion chemotherapy].

Complications of arterial infusion chemotherapy were analyzed in 261 cases from December 1983 to December 1993 in our department. Their complications involved nausea and vomiting (40.6%), bone marrow suppression (33.3%), liver dysfunction (20.3%), gastric and duodenal ulcer (9.6%) and so on. Complications involving an implantable device were hepatic arterial obstruction (29.1%), reservoir obstruction (5.7%), dislocation of catheter (4.6%), infection of catheter (3.8%), and obstruction of catheter (1.9%). In another cases with hepatic arterial obstruction, we performed arterial infusion in another artery as a bypass or stopped the infusion. In cases with obstruction of catheter not able to be reopened, we reinserted the catheter. An obstructed and/or infected reservoir was removed or replaced. Nausea and vomiting were found in 46.3% of FAM arterial infusion method (FAM) cases, in 53.3% of 5-FU persistent arterial method (5-FU) + FAM cases, and in 40.5% of intermittently persistent arterial method (IP) cases. Gastric and duodenal ulcer were noted in 9.8% of FAM, 13.3% of 5-FU + FAM, and 8.1% of IP cases. There were no significantly statistical differences between the methods. Hepatic arterial obstruction predominantly occurred in 32.4% of IP and 26.7% of 5-FU + FAM and bone marrow suppression was predominant in cases in which ADM was used. The duration of obstruction after administration was 154.0 +/- 117.4 days on average (21-455 days). Complications of hepatic arterial infusion chemotherapy are based on various causes which can be managed for prevention. We intend to enhance safety and assure the greater effectiveness of hepatic arterial chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Development of the sympathetic innervation to the cerebral arterial system in neonatal rats as revealed by anterograde labeling with wheatgerm agglutinin-horseradish peroxidase.

In order to clarify the developmental pattern in the sympathetic nerve fibers innervating the cerebral arterial system during the postnatal period in rats, we labeled the postganglionic nerve fibers originating in the superior cervical ganglion (SCG) and directly observed their extension and plexus formation by means of anterograde labeling with wheat germ agglutinin-horseradish peroxidase (WGA-HRP). The WGA-HRP solution was injected into the right SCG 1-7 days after birth. The rats were killed 48 h after trace injection, and the cerebral arteries were reacted with tetramethylbenzidine, then observed as a whole mount preparation. The labeled nerve fibers appeared as a few relatively straight bundles with branching fibers running longitudinally to the long axis of the artery in the ipsilateral right side of the circle of Willis and proximal portion of their main branching arteries at 3 days after birth. The nerve fibers started to form a circular pattern of nerve plexus only on the wall of the circle of Willis as early as 1 week after birth. At the beginning of postnatal week 2, labeled nerve fibers extended the collateral projections into the collateral side of the circle of Willis, and these expanding projections could not be observed at postnatal week 3. We observed a route of the sympathetic nerve fibers advancing into the cerebral arterial system which has not been described in previous studies; bundle of labeled nerve fibers entered into the wall of the middle portion of the basilar artery in half of the animals, in any postnatal period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Acadesine lowers temporal threshold for the myocardial infarct size limiting effect of preconditioning.

OBJECTIVE: The aim was to test the hypothesis that adenosine A1 receptor activation triggers the cardioprotective effects of ischaemic preconditioning, by determining whether pretreatment with acadesine (5-amino-4-imidazolecarboxamide riboside), an agent which increases cardiac adenosine level during ischaemia, could alter the threshold for preconditioning. METHODS: A branch of the left coronary artery of rabbit hearts was occluded for 30 min and reperfused for 3 h. Infarct size and risk zone size were determined with tetrazolium and fluorescent particles, respectively. Four groups were studied: untreated controls, a group which was pretreated with acadesine (2.5 mg.kg-1.min-1 for 5 min followed by 0.5 mg.kg-1.min-1 for 30 min ending 10 min prior to ischaemia), a group which was preconditioned with 2 min coronary branch occlusion + 10 min reperfusion, and a group which received pretreatment with acadesine prior to 2 min ischaemic preconditioning. RESULTS: Percent infarction, normalised as a percentage of the ischaemic zone, in the 2 min preconditioning group was 43.2(SEM 5.1)% which was not different from control [40.2(3.5)%]. Two minutes of preconditioning was not long enough to confer the cardioprotective effect of preconditioning. Acadesine alone had no protective effect on infarct size [38.5(4.5)%], but acadesine + 2 min preconditioning significantly limited infarction [18.1(2.7)%; p < 0.01]. CONCLUSIONS: Acadesine lowered the threshold for preconditioning in the rabbit to below 2 min of ischaemia. This observation supports the theory that endogenous adenosine which accumulates during the preconditioning ischaemia mediates the protective effects, and that this response can be augmented by acadesine.

Adenosine↗
PubMed1993

The protection of ischaemic preconditioning can be reinstated in the rabbit heart after the initial protection has waned.

OBJECTIVE: Preconditioning the heart with 5 min of ischaemia followed by reperfusion renders the myocardium resistant to infarction from subsequent ischaemia. This protection lasts for about 1 h. The aim of this study was to test whether the protection could be reinstated with a second episode of preconditioning after protection from an initial episode had worn off. METHODS: To induce infarction animals experienced 30 min of coronary artery occlusion and then 3 h reperfusion. Ischaemic preconditioning was accomplished with 5 min of coronary branch occlusion. In one group of rabbits the subsequent reperfusion period was prolonged to 2 h to permit protection to wear off before the 30 min coronary occlusion was initiated. In another group a second 5 min coronary occlusion was performed at the end of the 2 h reperfusion. After 10 min of reperfusion the 30 min ischaemic period began. Control animals experienced only the 30 min ischaemia and 3 h reperfusion. Infarct volume was measured with tetrazolium and expressed as a percentage of the ischaemic zone volume. RESULTS: Average infarct size in seven control rabbits [36.0 (SEM 2.0)% of the ischaemic zone] was not significantly different from that in eight rabbits with the prolonged coronary occlusion occurring 2 h after the preconditioning stimulus [28.6 (2.9)% infarction]. In contrast infarcts were significantly smaller in the re-preconditioned group of seven rabbits [8.3 (4.2)%] and comparable to those previously seen with a single preconditioning stimulus followed 10 min later by the 30 min occlusion [6.1 (1.8)%]. CONCLUSIONS: The rabbit heart can be protected with a second preconditioning stimulus after protection from an initial period of preconditioning has subsided.

Animals↗
PubMed1993

Pretreatment with the adenosine A1 selective agonist, 2-chloro-N6-cyclopentyladenosine (CCPA), causes a sustained limitation of infarct size in rabbits.

OBJECTIVE: The highly selective adenosine A1 receptor agonist, 2-chloro-N6-cyclopentyl-adenosine (CCPA), has been shown to be as cardioprotective as ischaemic preconditioning when evaluated with an early staining method using tetrazolium. However, tetrazolium-positive tissue measured 3 h after reperfusion may still overestimate the long term salvage. To test for this possible artefact, a 72 h reperfusion rabbit model of myocardial infarction was used, and infarct size was assessed by histology. METHODS: Myocardial infarction was induced by a 30 min coronary occlusion. Rabbits were assigned to a control group receiving no treatment, pretreatment with 0.125 mg.kg-1 CCPA, or 0.25 mg.kg-1 pretreatment with CCPA (0.25 mg.kg-1) followed by an A1 selective antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) 30 min after reperfusion to reverse the haemodynamic side effects. RESULTS: In the 0.125 mg.kg-1 CCPA group, 30.8(SEM 4.2)% of the ischaemic zone was infarcted, which was significantly less than that seen in the control group [46.5(3.0)%; p < 0.01]. Reversing the side effects of CCPA by giving DPCPX soon after reperfusion did not block the protective effects [26.2(1.9)% infarction; p < 0.01 v control]. CONCLUSIONS: This finding confirms a genuine anti-infarct effect of adenosine A1 receptor stimulation when given prior to the onset of ischaemia. Furthermore blocking the A1 receptors soon after reperfusion reverses the side effects but does not block protection.

Adenosine↗
PubMed1993

The kinetics of lymphocyte subsets and macrophages in subarachnoid space after subarachnoid hemorrhage in rats.

BACKGROUND AND PURPOSE: Although it has been suggested that humoral immunity plays a role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage, there has been no quantitative assay for cellular immunity. We studied the kinetics of immune cells in the subarachnoid space after subarachnoid hemorrhage in the rat. METHODS: One hundred fourteen Sprague-Dawley rats were used in this study. The animals were divided into two groups and injected with either autologous blood (0.3 mL) or saline into the major cistern. They were killed at the specified time: 10 minutes or 1, 2, 3, 5, or 7 days after subarachnoid hemorrhage. For immunohistochemical analysis, the rats' whole brains were frozen, and cryostat sections were prepared. For flow cytometric analysis of immune cell presence, their whole brains underwent enzymatic digestion. RESULTS: Histopathologic study revealed pathological change of the arterial wall, and immunohistochemical study revealed the existence of macrophages and T cells in the subarachnoid space in animals with a survival time of 2 to 5 days after subarachnoid hemorrhage. A flow cytometric study revealed the peak of appearance of T cells and macrophages 2 days after subarachnoid hemorrhage. The helper-suppressor T cell ratio also reached a peak 2 days after subarachnoid hemorrhage. CONCLUSIONS: A serial response of immunoreactive cells, which resembles that of the chronic allergic reaction observed in autoimmune diseases or delayed-type hypersensitivity, exists in the subarachnoid space after subarachnoid hemorrhage. The present results suggest that the initial response in cellular immunity, which is followed by humoral immunity and eicosanoid reactions, plays a role in eliciting the development of cerebral vasospasm.

Animals↗
PubMed1993

Effect of systemic hypotension on cerebral energy metabolism during chronic cerebral vasospasm in primates.

The influence of systemic hypotension on cerebral blood flow (CBF) and energy metabolism during chronic cerebral vasospasm after subarachnoid hemorrhage was studied in 15 monkeys. Changes in the phosphorus spectrum, as demonstrated by in vivo phosphorus-31 (31P) magnetic resonance (MR) spectroscopy, or in regional CBF were measured in the parietal cortex during graded hypotension. Sequential changes in the phosphorus spectrum were observed during moderate hypotension in the animals 7 days after the introduction of an autologous blood clot around the right middle cerebral artery (MCA). Angiograms revealed a reduction in vessel caliber by approximately 50% in the right MCA. The mean CBF in the spasm side decreased in parallel with a decrease in the mean arterial blood pressure (MABP) from 120 to 40 mm Hg, indicating the abolition of autoregulation. There were no significant differences in the mean percentage totals of inorganic phosphate (Pi), phosphocreatine (PCr), adenosine triphosphate (ATP), and pH between the hemispheres at baseline MABP before hypotension. The values of PCr, ATP, and pH decreased significantly (p < 0.05) and Pi increased significantly (p < 0.05) at an MABP of less than 60 mm Hg in the involved hemisphere. The ratio of PCr:Pi decreased in parallel with a decrease in MABP. The ATP showed a stepwise decrease during moderate hypotension (MABP 60 mm Hg) and was reduced significantly 20 minutes after the beginning of hypotension (p < 0.05). The results indicate that, during chronic vasospasm, changes in cerebral energy metabolism are coupled with changes in CBF in the state of impaired autoregulation. There exists a critical level for ischemia below which high-energy phosphorus metabolites become markedly depleted. It is suggested that 31P MR spectroscopy may be useful to evaluate the ischemic vulnerability of brain tissue in order to prevent delayed neurological deficit during cerebral vasospasm.

Animals↗
PubMed1993

Evaluation of intraplatelet and urinary 5-hydroxytryptamine (5-HT), and urinary 5-hydroxyindoleacetic acid (5-HIAA) levels in patients with toxemia of pregnancy.

Toxemia of pregnancy is considered to represent a disorder of activated blood coagulation. To identify possible indicators for evaluating the clinical course of toxemia, we measured the intraplatelet and urinary levels of 5-HT and its urinary metabolite, 5-HIAA in 25 patients with toxemia vs. 29 non-toxemic pregnant women. 5-HT and 5-HIAA were assayed by high performance liquid chromatography (HPLC). During the 24-34 weeks of gestation, the toxemic patients and the non-toxemic women each had low intraplatelet levels of 5-HT which didn't differ significantly. A significant (p < 0.05) decrease in intraplatelet 5-HT was observed in the toxemic patients vs. the non-toxemic women after the 35th week of gestation until delivery. The untake of exogenous 5-HT by platelets was increased in the toxemic patients, and their urinary (5-HT+5-HIAA) value increased significantly (p < 0.05) as compared with the non-toxemic women after the 35th week of gestation until delivery. A decrease in the intraplatelet level of 5-HT and an increase in the urinary level of (5-HT+5-HIAA) were observed in the toxemic patients, findings that paralleled the progression of this disorder. Serial measurements of intraplatelet and urinary levels of 5-HT and urinary levels of 5-HIAA in the toxemic patients revealed a significant correlation between disease activity and those levels. These observations support the concept that the measurement of intraplatelet and urinary levels of 5-HT and of urinary levels of 5-HIAA may be useful in following the clinical course of the toxemic patients.

Adult↗
PubMed1993

[A case report of atypical Fabry's disease with colon cancer].

An atypical case of Fabry's disease, a rare congenital disorder of glyco-lipid metabolism, associated with sigmoid cancer was reported. A 50-year-old man who had been diagnosed as having atypical form of Fabry's disease complained of lower abdominal pain and difficult defection. A barium enema and an endoscopic examination disclosed sigmoid colon cancer. The cancer was curatively resected. Fabry's disease is often associated with intestinal disease, but the patient with Fabry's disease associated with intestinal malignancy has not been reported.

Adenocarcinoma↗
PubMed1992

Tumor necrosis factor production during human renal allograft rejection is associated with depression of plasma protein C and free protein S levels and decreased intragraft thrombomodulin expression.

Fibrin deposition is a common accompaniment of renal allograft rejection, indicating disruption of the normal physiologic balance between procoagulant and anticoagulant pathways. In vitro, tumor necrosis factor (TNF) induces endothelial expression of the procoagulant, tissue factor, and downregulation of thrombomodulin, a key component of the thrombomodulin/protein C (PC)/protein S (PS) pathway, which normally maintains an anticoagulant state by inactivating thrombin, preventing further thrombin formation by degrading factors Va and VIIIa, and decreasing plasminogen activator inhibitor activity. Raised levels of TNF were recently demonstrated within the blood of patients during episodes of renal allograft injection, and may be an early and discriminatory marker of rejection. This led us to investigate prospectively whether monitoring of serum TNF levels was of value clinically, and was associated with effects on circulating PC and PS levels, or alterations in intragraft thrombomodulin expression. Plasma samples (n = 454) were collected three times/week from all patients (n = 25) undergoing renal transplantation during a 9-month consecutive period, and assayed by ELISA and functional assays for TNF, PC, and free PS (FPS). Portions of renal biopsies, taken to evaluate episodes of acute deterioration of renal function, were evaluated by immunoperoxidase labeling for the presence and distribution of TNF, thrombomodulin, PC, PS, thrombin, fibrin, and factors V and VIII. Comparison of 78 plasma samples collected during 26 episodes of biopsy-proven acute cellular rejection with samples collected during periods of stable renal function (n = 349) showed that TNF levels rose significantly (390 +/- 242 pg/ml, p less than 0.01) above background levels 3 days before rising serum creatinine concentrations, and peaked (2,426 +/- 978 pg/ml) on the day of clinical rejection. PC-antigen (Ag) concentrations also decreased 3 days before rejection (68 +/- 13%, p less than 0.05), and were maximally depressed (49% +/- 16%, p less than 0.001) on the day of rejection. FPS levels were normal until the day before rejection (63% +/- 8%, p less than 0.01) and, like PC, were maximally depressed (43 +/- 10%) at rejection. Plasma TNF levels were significantly and inversely correlated with PC-Ag (p less than 0.001) and FPS (p less than 0.005) levels during rejection, regardless of whether such rejection episodes were steroid responsive or required OKT3 monoclonal antibody therapy. TNF, PC, and FPS levels were normal during episodes of cyclosporine toxicity and viral infection.(ABSTRACT TRUNCATED AT 400 WORDS)

Biomarkers↗
PubMed1992

Role of adenosine receptor activation in myocardial infarct size limitation by ischaemic preconditioning.

OBJECTIVE: The aims were to examine the role of adenosine receptors in the mechanism of preconditioning in a chronic rabbit model of myocardial infarction; to assess whether the preconditioning effect is blocked by an adenosine receptor antagonist, 8-phenyltheophylline; and to determine whether an adenosine A1 receptor agonist, R(-)N6-2-phenylisopropyl adenosine (R-PIA), mimics infarct size limitation by preconditioning. METHODS: Myocardial infarction was induced in male rabbits by occlusion of the left coronary artery for 30 min, which was followed by 72 h reperfusion. Before the 30 min ischaemia, rabbits were subjected to one of the following six protocols: (1) untreated control; (2) intravenous injection of 8-phenyltheophylline; (3) preconditioning with 5 min ischaemia; (4) pretreatment with 8-phenyltheophylline plus preconditioning; (5) intravenous injection of R-PIA; or (6) R-PIA plus atrial pacing (240.min-1). Infarct size and area at risk were determined by histology and fluorescent particles, respectively. RESULTS: Preconditioning significantly limited infarct size, normalised as a percent of area at risk (%IS/AR), to 19.2 (SEM 2.3)% v control value of 46.5(2.8)%. 8-Phenyltheophylline alone did not modify the %IS/AR, but its injection before preconditioning attenuated the preconditioning effect such that IS/AR = 34.4(2.5)%. While R-PIA did not achieve statistically significant myocardial salvage, R-PIA plus atrial pacing limited infarct size to 33.7(3.0)% (p<0.05 v control). The R-PIA group had severe hypotension and their infarct sizes were inversely correlated with diastolic blood pressure at reperfusion. There was no such correlation in the R-PIA plus pacing group in which bradycardia and hypotension induced by R-PIA were attenuated by atrial pacing. CONCLUSIONS: The infarct size limiting effect of preconditioning was attenuated by 8-phenyltheophylline, and pretreatment with R-PIA was able to limit myocardial infarct size when severe hypotension was avoided by atrial pacing. These findings suggest that adenosine receptor activation plays a crucial role in the mechanism of preconditioning.

Animals↗
PubMed1992

Effect of anoxic preperfusion on ischemic myocardial injury in isolated rat hearts.

Anoxic perfusion prior to sustained ischemia (anoxic preperfusion), reportedly improves postischemic functional recovery of the heart, but its mechanism has not been well understood. The present study aimed to characterize the cardioprotective effects of anoxic preperfusion and its relationship to extracellular Ca++ levels. Following 10 min of aerobic perfusion, isolated rat hearts were assigned to a 10 min aerobic perfusion or to a 10 min anoxic perfusion. The hearts were then subjected to 30 min of global ischemia and 30 min of aerobic reperfusion. When the perfusate-free Ca++ concentration was 2.0 mM, postischemic recovery of left ventricular developed pressure was significantly improved by anoxic preperfusion (91.9 +/- 2.9% of baseline value vs. 50.5 +/- 12.9% after 30 min reperfusion in the controls). However, the improvement of postischemic ventricular function by anoxic preperfusion was abolished when perfusate Ca++ was reduced to 1.0 mM and the contractile function was rather suppressed during early reperfusion by anoxic preperfusion when the Ca++ level was 0.7 mM (87.5 +/- 11.8% vs. 115.6 +/- 13.9% after 10 min of reperfusion). On the other hand, lactate accumulation during the global ischemia was significantly less in anoxic preperfused hearts compared with untreated hearts both when perfusate Ca++ was 0.7 mM (61.3 +/- 5.1 vs. 85.9 +/- 6.8 mumol/g dry) and when it was 2.0 mM (43.8 +/- 2.0 vs. 140.3 +/- 14.1 mumol/g dry). The amount of myoglobin released after global ischemia was not different between untreated and anoxic preperfused hearts regardless of the perfusate Ca++ level. The results suggest that anoxic preperfusion does not reduce ischemic myocardial necrosis, but it attenuates myocardial stunning. That effect of anoxic preperfusion on the stunning is dependent on the extracellular Ca++ level and is not totally explained by suppression of ischemia-induced lactate accumulation.

Adenosine Triphosphate↗
PubMed1992

Scintigraphy in gastroesophageal reflux disease: a comparison to endoscopy, LESp, and 24-h pH score, as well as to simultaneous pH monitoring.

We compared scintigraphy to other reflux tests in 45 symptomatic patients. Sensitivity of 24-h pH score was 82%, endoscopy 64%, and LESp 33%. Scintigraphy was insensitive (36%), although 50% of patients with esophagitis had a positive test. Specificity and positive predictive value were good (all greater than or equal to 88%) in discerning patients with an abnormal 24-h pH score and esophagitis. We suggest scintigraphy as the first diagnostic test to confirm frequent reflux events (REs) and normal clearance in the subgroup of patients with severe endoscopic esophagitis, and manometry and 24-h pH monitoring when scintigraphy is negative. We also compared scintigraphy to simultaneously performed pH monitoring in detecting individual postprandial REs and their clearance. The two methods agreed in only 25% of total reflux events. Scintigraphy was superior at detection of reflux of buffered gastric contents and detection of additional REs during acid clearing intervals, whereas only the pH probe detected REs after gastric emptying. We conclude that scintigraphy has a limited role as a diagnostic test in gastroesophageal reflux disease, and much potential as a research tool, especially in combination with the pH probe.

Adult↗
PubMed1991

Disposition of single-dose intravenous and oral aspirin in children.

We described the pharmacokinetics of acetylsalicylic acid and salicylic acid in 5 children with prior Kawasaki disease receiving buffered aspirin tablets or intravenous aspirin DL-lysine. Oral aspirin is characterized by its longer mean residence time in the body (MRT), an indicator for duration of exposure, than intravenous aspirin (1.18 vs. 0.37 h). The apparent elimination half-life (t1/2) of acetylsalicylic acid was also longer after oral than after intravenous administration of aspirin (40 vs. 17 min). The mean absorption time was calculated to be as long as 0.8 h. In contrast, the two modes of administration gave virtually identical results regarding MRT of salicylic acid proper and its t1/2. After oral administration of aspirin, 51% of the dose is absorbed intact as acetylsalicylic acid while 23% is converted to salicylic acid presystemically, indicating that 74% of aspirin is actually absorbed. Our data suggest that an equivalent intravenous aspirin dose to achieve the same salicylic acid concentration is about 70% of the oral dose. However, the area under the curve of acetylsalicylic acid itself, a more potent cyclooxygenase inhibitor than salicylic acid, would be about 1.5 times higher than that following oral administration. The clinical consequences of this exposure difference remain uncertain.

Absorption↗