You can find all the information on the official websites FDA and EMA in pre-clinical research guidelines. It depends on the type and structure of your material.

Thank you for your attention. I'm trying to compare urinary pharmacokinetics of available Cephalosporin antibiotics. I've already gone trough FDA guideline but I need some published paper on it.

Dear Kushal,

The following publication contains a protocol which may be helpful to be applied for your study design:

Study design

The kinetic studies after single oral dosing with 100 mg of cefdinir were carried out in patients with chronic renal failure with and without hemodialysis for 4 h. Two tests were performed separately 4 weeks apart, and the test without hemodialysis was started first. Cefdinir was given 30 min after breakfast (601 kcal of energy, 31 g of protein, 16.3 g of lipid, and 79 g of carbohydrate). Blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h (samples at 10 and 72 h were added in the test with hemodialysis) after drug administration. In the test with dialysis, hemodialysis was started 8 h after drug administration, since the median Tmax in the test without dialysis was 8 h. Blood was centrifuged to separate the plasma, and plasma was stored at −20°C until being assayed. The concentrations of cefdinir in plasma were measured by high-performance liquid chromatography (HPLC) at Mitsubishi Kagaku Bio-Clinical Laboratories, Inc. (Tokyo, Japan). Plasma (0.5 ml) was mixed with 1/15 M phosphate-buffered saline (pH 7.0) (0.05 ml) with an internal standard solution (0.05 ml) of ceftizoxime sodium. The mixture was vortexed for 5 s with 1 M H3PO4 (0.4 ml). The mixture solution (0.9 ml) was transferred to Bond Elut SCX (100 mg) (GL Science, Tokyo, Japan) for 30 s and preconditioned with methanol (0.2 ml), followed by distilled water (1.0 ml). The column was washed by eluting with 0.01 N HCl (2 ml), followed by distilled water (1.0 ml). Cefdinir was eluted from the column with 0.2 M Na2HPO4 (1.0 ml). The eluent was collected in a tube, and aliquots (50 μl) were applied to HPLC. An LC-6AD high-performance liquid chromatograph (Shimazu, Kyoto, Japan) equipped with a spectrophotometric detector, SPD-10AV (Shimazu), was used. The column, 25 cm long and 4.6 mm in inner diameter, was packed with TSKgel ODS-80TM (Tosoh, Tokyo, Japan). The mobile phase for cefdinir was citrate buffer (pH 2.5)–acetonitril at a flow rate of 1.2 ml/min, and the effluent was monitored at 280 nm. The detection limit for cefdinir was 0.05 μg/ml, and the coefficients of variation on samples of 0.05, 0.10, 1.001, and 5.005 μg of cefdinir per ml were 13.12, 13.84, 2.13, and 4.77%, respectively. The coefficients of day-to-day variation on samples of 0.10, 1.001, and 5.005 μg/ml were 9.64, 2.27, and 4.75%, respectively. Day-to-day precision was 1.03 to 6.27%.

Pharmacokinetic analysis

Pharmacokinetic parameters were calculated by a model-independent method.Cmax and Tmax were determined by plasma concentration-time data, and the elimination rate constant (β) was determined by linear least-squares regression analysis. The terminal elimination half-life (t1/2) was calculated as ln 2/β. t1/2 during hemodialysis was determined by data at 8, 10, and 12 h in the test with dialysis, and post-hemodialysis t1/2 was calculated from plasma cefdinir concentrations at 12, 24, and 48 h.

Plasma cefdinir area under the concentration-time curve from time zero to infinity (AUC0–∞) was estimated by using the plasma concentrations from time zero to the last time measured by the trapezoidal rule for time zero to the last measurement and then extrapolating to infinity by adding the last measured plasma concentration divided by β.

The fractional removal of cefdinir (fd) by hemodialysis was calculated by the equation fd = [1 −t1/2(HD)/t1/2] × [1 − exp (−0.603)/t1/2 (HD)] × 100, where t1/2 (HD) is t1/2 in the test with hemodialysis andt1/2 is t1/2 in the test without dialysis.

During hemodialysis, cefdinir, creatinine, urea nitrogen levels, as well as hematocrit, were determined in plasma from both venous and arterial lines. The hemodialysis CL of these items was calculated by the equation CL (ml/min) = QB [(B − V)/B] (1 − Ht), where QB is the dialyzer blood flow rate, B is the concentration in plasma (μg/ml) in arterial lines, V is the concentration in plasma (μg/ml) in venous lines, and Ht is hematocrit.

Statistical analysis

Results are expressed as means ± standard deviations (SD). For statistical comparisons, a paired t test was used; a P value of less than 0.05 was considered significant statistically.

This text was taken from a paper entitled "Pharmacokinetic Study of an Oral Cephalosporin, Cefdinir, in Hemodialysis Patients " published in Antimicrob Agents Chemother. 1998 Jul; 42(7): 1718–1721.

To view the full publication, please use the following link:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC105672/

In addition, the following is a review article that may be helpful since it provides a comprehensive overview of cephalosporin pharmacokinetcs:

Clinics (Sao Paulo). 2011 Jul; 66(7): 1267–1274.

doi:  10.1590/S1807-59322011000700024

PMCID: PMC3148475

Pharmacokinetics of cephalosporins in the neonate: a review

Gian Maria Pacifici

Author information ► Article notes ► Copyright and License information ►

This article has been cited by other articles in PMC.

Abstract

The aim of this work was to review the published data on the pharmacokinetics of cephalosporins in neonates to provide a critical analysis of the literature as a useful tool for physicians.

The bibliographic search was performed for articles published up to December 3, 2010, using PubMed. In addition, the book Neofax: A Manual of Drugs Used in Neonatal Care by Young and Mangum was consulted.

The cephalosporins are mainly eliminated by the kidneys, and their elimination rates are reduced at birth. As a consequence, clearance is reduced and t1/2 is more prolonged in the neonate than in more mature infants. The neonate's substantial body water content creates a large volume of distribution (Vd) of cephalosporins, as these drugs are fairly water soluble. Postnatal development is an important factor in the maturation of the neonate, and as postnatal age proceeds, the clearance of cephalosporins increases. The maturation of the kidney governs the pharmacokinetics of cephalosporins in the infant. Clearance and t1/2 are influenced by development, and this must be taken into consideration when planning a cephalosporin dosage regimen for the neonate.

Keywords: Cephalosporins, Pharmacokinetics, Neonate

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INTRODUCTION

Cephalosporins are the most common class of antibiotics used to treat bacterial infection. These drugs have proven to be safe, clinically effective, and easy to use.1,2 The expanded-spectrum cephalosporins (e.g., cefotaxime, ceftriaxone, and ceftazidime), either alone or in combination with other antibiotics, are the most common antibiotics used as initial empiric therapy for treating serious infections.3

The first generation of cephalosporins has good activity against Gram-positive bacteria and relatively modest activity against Gram-negative bacteria. The second generation of cephalosporins has increased activity against Gram-negative microorganisms but tends to be much less active than the third-generation agents. The fourth generation of cephalosporins is particularly useful for the empirical treatment of serious infections in hospitalized patients when Enterobacteriaceae and pseudomonas are potential etiologies.4 Cephalosporins are minimally toxic, with the exception of ceftriaxone, which displaces bilirubin from albumin5,6 and precipitates calcium, resulting in serious adverse effects.7,8 The aim of this paper was to review the literature on the kinetics of cephalosporins in the neonate and provide a critical analysis of the literature as a useful tool for physicians.

Bibliographic search

The bibliographic search was performed electronically, using PubMed to find articles published up to December 3, 2010. First, a Medline search was performed with the key words “pharmacokinetics of cephalosporins in neonates," with the limit of “human”. Other Medline searches were performed with the key words “pharmacokinetics of ……… in neonates,” followed by the names of single cephalosporins. In addition, the book Neofax: A Manual of Drugs Used in Neonatal Care by Young and Mangum9 was consulted. The bibliographic search produced 37 original articles, four review articles and two book chapters. The publication years of this material ranged from 1977 to 2010.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148475/

Hoping this will be helpful,

Rafik

Thank you Dr. Karaman. It will be a huge support to me, 

Thank you Dr. Jun Shi. It will be a great support to my research.