Oral Paracetamol Bioavailability in Rats Subjected to Experimental Spinal Cord Injury

Garcı́a-López, Patricia; Pèrez‐Urizar, José; Madrazo, Ignacio; Guı́zar-Sahagún, Gabriel; Castañeda‐Hernández, Gilberto

doi:10.1002/(sici)1099-081x(199704)18:3<203::aid-bdd11>3.0.co;2-f

Cited by 11 publications

(8 citation statements)

References 27 publications

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“…The oral bioavailability of paracetamol, 8 salycilates, 9 and cyclosporin 10 is reduced after experimental SCI. These alterations are more evident during acute stage and the reduction in oral bioavailability is likely due to an impaired gastric emptying.…”

Section: Introductionmentioning

confidence: 95%

Acute spinal cord injury changes the disposition of some, but not all drugs given intravenously

Garcı́a-López

Martínez-Cruz²,

Guı́zar-Sahagún

et al. 2006

Spinal Cord

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Study design: Experimental laboratory investigations in paraplegic rats. Objective: In order to understand why acute spinal cord injury (SCI) changes the disposition of some, but not all drugs given intravenously (i.v.), pharmacokinetic parameters of drugs with different pharmacological properties were evaluated to determine the influence of SCI on physiological processes such as distribution, metabolism and excretion. Setting: Mexico City, Mexico. Methods: Rats were subjected to severe SCI (contusion) at T-9 level; pharmacokinetic studies of phenacetin, naproxen or gentamicin were performed 24 h after. These drugs were not chosen as markers because of their therapeutic properties, but because of their pharmacokinetic characteristics. Additional studies including plasma proteins, liver and renal function tests, and micro-vascular hepatic blood flow, were also performed at the same time after injury. Results: Acute SCI significantly reduced distribution of drugs with intermediate and low binding to plasma proteins (phenacetin 30% and gentamicin 10%, respectively), but distribution did not change when naproxen -a drug highly bound to plasma proteins (99%) -was used, in absence of changes in plasma proteins. Metabolism was significantly altered only for a drug with liver blood flow -limited clearance (phenacetin) and not for a drug with liver capacity-limited clearance (naproxen). The liver function test did not change, whereas the hepatic micro-vascular blood flow significantly decreased after SCI. Renal excretion, evaluated by gentamicin clearance, was significantly reduced as a consequence of SCI, without significant changes in serum creatinine. Conclusions: Changes in drug disposition associated to acute SCI are complex and generalization is not possible. They are highly dependent on each drug properties as well as on the altered physiological processes. Results motivate the quest for strategies to improve disposition of selective i.v. drugs during spinal shock, in an effort to avoid therapeutic failure.

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Section: Introductionmentioning

confidence: 95%

Acute spinal cord injury changes the disposition of some, but not all drugs given intravenously

Garcı́a-López

Martínez-Cruz²,

Guı́zar-Sahagún

et al. 2006

Spinal Cord

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“…Given the diversity of the meals ingested every day, it is impossible to determinate exactly the time necessary for a drug to pass through the pylorus and this phenomenon could be considered as a random event [60]. acetaminophen is totally (F ¼ 80-90%) [70,71] and rapidly absorbed (t max ¼ 12-19 min) [33,72] through the intestinal wall by passive diffusion [73], and so consequently its absorption profile depends directly on the rate of gastric emptying. acetaminophen is totally (F ¼ 80-90%) [70,71] and rapidly absorbed (t max ¼ 12-19 min) [33,72] through the intestinal wall by passive diffusion [73], and so consequently its absorption profile depends directly on the rate of gastric emptying.…”

Section: Animal Modelsmentioning

confidence: 99%

The influence of weightlessness on pharmacokinetics

Gandia

Saivin

Houin

2005

Fundamemntal Clinical Pharma

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The primary hostile factor during a spaceflight is the lack of gravity, which can induce space motion sickness and act on bones, muscles and the cardiovascular system. These physiological effects may modify the pharmacokinetics of the drugs administered during the flight producing reduced pharmacological activity or appearance of adverse effects. Given the small number of spaceflights and the difficulties of conducting experiments during missions, pharmacokinetic data obtained in flight are insufficient to determine if drug monitoring is necessary for the drugs present in the onboard medical kit. Therefore, validated earthbound models like tail-suspension performed with animals and long-term bedrest performed with human volunteers are used to simulate weightlessness and to study the pharmacokinetic variations of either absorption, distribution, or elimination of drugs. As a result of these studies, it is possible to make some dosing recommendations but more information is necessary to predict with precision all of the pharmacokinetic variations occurring in spaceflight. To collect more pharmacokinetic information, head-down bedrest studies are still the best solution and as saliva is an appropriate substitution for plasma for some drugs, salivary sampling can be planned during flights.

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“…Life threatening complications such as pneumonia, urinary tract infections and infected pressure sores are commonplace, mainly at the early stages of the lesion, despite the use of standard pharmacological treatment1–3. It is possible that such therapeutic failures are due, at least in part, to unsuitable dosing strategies which don't consider pharmacokinetic alteration in this patient population4. SCI may change the kinetics of drug absorption, distribution and elimination5.…”

mentioning

confidence: 99%

“…Such characterization, however, is highly difficult to perform in human subjects, give the high inter-individual variability observed in clinical situation. Therefore pharmacokinetic studies using experimental model of SCI appear to be the most suitable strategy4. Amitriptyline was studied because it is widely used for treatment of pain in SCI patients15, and some evidence suggest that one of the most effective agent in treatment of neuropathic pain due to SCI is amitriptyline.…”

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confidence: 99%

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Amitriptyline pharmacokinetics in experimental spinal cord injury in the rabbit

et al. 2008

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Previous studies have demonstrated that pharmacokinetic behavior of several drugs such as paracetamol, theophylline, and aminoglycosides are significantly altered in spinal cord injured patients. No pharmacokinetic study of amitriptyline has been performed in patients and experimental models of spinal cord injury. Pharmacokinetic parameters of amitriptyline in orally treated rabbits subjected to laminectomy and spinal cord injury compared with those underwent laminectomy alone. Among twenty four male rabbits were included in this study, nine of them subjected to spinal cord injury at the 8th thoracic level by knife severance method and six rabbits underwent laminectomy alone (sham group) and nine rabbits treated as control. All received a single oral dose of amitriptyline (20 mg/kg) 24 h after injury. Blood sampling were done at predetermined times to 36 h after drug administration. Amitriptyline concentration in serum samples was determined by high-performance liquid chromatography. Pharmacokinetic parameters including maximum concentration (Cmax), time to reach maximum concentration (Tmax), half life, and the area under the curve to last detectable concentration time point (AUC0-t) were directly determined from the concentration-time curve. Maximum concentration was observed at 6.5 h after administration in sham group with a concentration of 439.6 ng/ml, whereas in SCI group Tmax was at 2.7 h with a concentration of 2763.9 ng/ml. In control group it was 3.3 h and 396 ng/ml, respectively. In SCI group, AUC was 9465.6 ng.h/ml and half life was 6 h and for control group it was 2817.4 ng.h/ml and 6.4 h, respectively. Statistical analysis of data showed that SCI didn't induce significant changes in amitriptyline pharmacokinetic parameters.

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Oral Paracetamol Bioavailability in Rats Subjected to Experimental Spinal Cord Injury

Cited by 11 publications

References 27 publications

Acute spinal cord injury changes the disposition of some, but not all drugs given intravenously

Acute spinal cord injury changes the disposition of some, but not all drugs given intravenously

The influence of weightlessness on pharmacokinetics

Amitriptyline pharmacokinetics in experimental spinal cord injury in the rabbit

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