Determination of free ceftriaxone concentration and its application in predicting lung tissue concentration

doi:10.5246/jcps.2021.07.046

Abstract

Abstract:

The purpose of this study was to establish a method for determining the free concentration of ceftriaxone based on hollow fiber centrifugal ultrafiltration (HFCF-UF) technology in combination with high-performance liquid chromatography (HPLC) for free pharmacokinetic studies and the prediction of ceftriaxone concentrations in lung tissue. This method only required centrifugation for a short time, and the filtrate could be injected directly for HPLC analysis without further treatment. The specificity, linearity, precision and stability of this method were validated for quantification of free ceftriaxone. Under the optimized conditions, the absolute recoveries were more than 92.5%. The intraday and interday precision RSDs were less than 3.6%. Additionally, nonspecific adsorption (NSB) between the analyte and the ultrafiltration membrane was considered. This method was successfully applied to the analysis of the free ceftriaxone concentration in rat plasma and lung tissue. The free ceftriaxone concentration of lung tissue could be predicted by using the linear formula C_fl = C_fp (0.342x – 0.0129) (x: time). This method also provides a reliable alternative for accurate monitoring of the free ceftriaxone concentration in therapeutic drug monitoring (TDM).

Key words: Ceftriaxone, Free tissue concentration, Hollow fiber centrifugal ultrafiltration, Pharmacokinetics

Supporting:

Yanan Li, Xue Guo, Ye Yuan, Weichong Dong, Xiuling Yang. Determination of free ceftriaxone concentration and its application in predicting lung tissue concentration[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(7): 578-589.

Figures/Tables 14

Table 1. Linear ranges and tested concentrations of ceftriaxone.

Table 2. Linear ranges, LODs and LOQs of free ceftriaxone analysis in plasma and lung tissue.

Table 3. Results of recovery and precision tests of free ceftriaxone.

Table 4. The stability of ceftriaxone in plasma under various conditions (n = 5).

Table 5. The stability of ceftriaxone in lung tissue under different conditions (n = 5).

Table 6. The free plasma ceftriaxone concentration in rats at different time (n = 20).

Table 7. PK parameters of free ceftriaxone (mean ± SD) in rats after receiving ceftriaxone.

Table 8. Free ceftriaxone concentration in plasma and lung tissue at different time.

Table 9. Results of analyte recovery with four kinds of hollow fibers.

References 17

[1]	Vincent, J.L.; Rello, J.; Marshall, J.; Silva, E.; Anzueto, A.; Martin, C.D.; Moreno, R.; Lipman, J.; Gomersall, C.; Sakr, Y.; Reinhart, K.; Investigators, E.I.G.O. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009, 302, 2323–2329.
[2]	Wong, G.; Briscoe, S.; Adnan, S.; McWhinney, B.; Ungerer, J.; Lipman, J.; Roberts, J.A. Protein binding of β-lactam antibiotics in critically ill patients: can we successfully predict unbound concentrations? Antimicrob. Agents. Chemother. 2013, 57, 6165–6170.
[3]	Zhou, J.J.; Bai, Y.J.; Wang, X.; Yang, J.; Fu, P.; Cai, D.M.; Yang, L.C. A simple risk score for prediction of sepsis associated-acute kidney injury in critically ill patients. J. Nephrol. 2019, 32, 947–956.
[4]	Sime, F.B.; Stuart, J.; Butler, J.; Starr, T.; Wallis, S.C.; Pandey, S.; Lipman, J.; Roberts, J.A. A pharmacokinetic case study of intravenous posaconazole in a critically ill patient with hypoalbuminaemia receiving continuous venovenous haemodiafiltration. Int. J. Antimicrob. Agents. 2018, 52, 506–509.
[5]	Zelenitsky, S.A.; Ariano, R.E.; Zhanel, G.G. Pharmacodynamics of empirical antibiotic monotherapies for an intensive care unit (ICU) population based on Canadian surveillance data. J. Antimicrob. Chemother. 2011, 66, 343–349.
[6]	Udy, A.A.; Varghese, J.M.; Altukroni, M.; Briscoe, S.; McWhinney, B.C.; Ungerer, J.P.; Lipman, J.; Roberts, J.A. Subtherapeutic initial β-lactam concentrations in select critically ill patients: association between augmented renal clearance and low trough drug concentrations. Chest. 2012, 142, 30–39.
[7]	Kovar, A.; Costa, T.D.; Derendorf, H. Comparison of plasma and free tissue levels of ceftriaxone in rats by microdialysis. J. Pharm. Sci. 1997, 86, 52–56.
[8]	Tsai, D.; Stewart, P.; Goud, R.; Gourley, S.; Hewagama, S.; Krishnaswamy, S.; Wallis, S.C.; Lipman, J.; Roberts, J.A. Total and unbound ceftriaxone pharmacokinetics in critically ill Australian Indigenous patients with severe sepsis. Int. J. Antimicrob. Agents. 2016, 48, 748–752.
[9]	Roberts, J.A.; Lipman, J. Pharmacokinetic issues for antibiotics in the critically ill patient. Crit. Care Med. 2009, 37, 840–851. quiz859.
[10]	Neves, D.V.; Vieira, C.P.; Rocha, A.; Lanchote, V.L. Therapeutic doses of eltrombopag do not inhibit hepatic BCRP in healthy volunteers: intravenous ceftriaxone as a model. J. Pharm. Pharm. Sci. 2018, 21, 236–246.
[11]	Dong, W.C.; Zhang, J.F.; Hou, Z.L.; Jiang, X.H.; Zhang, F.C.; Zhang, H.F.; Jiang, Y. The influence of volume ratio of ultrafiltrate of sample on the analysis of non-protein binding drugs in human plasma. Analyst. 2013, 138, 7369–7375.
[12]	Li, J.M.; Shi, Q.W.; Jiang, Y.; Liu, Y. Pretreatment of plasma samples by a novel hollow fiber centrifugal ultrafiltration technique for the determination of plasma protein binding of three coumarins using acetone as protein binding releasing agent. J. Chromatogr. B. 2015, 1001, 114–123.
[13]	Kotani, A.; Hirai, J.; Hamada, Y.; Fujita, J.; Hakamata, H. Determination of ceftriaxone concentration in human cerebrospinal fluid by high-performance liquid chromatography with UV detection. J. Chromatogr. B. 2019, 1124, 161–164.
[14]	Zhao, Y.L.; Cudkowicz, M.E.; Shefner§, J.M.; Krivickas, L.; David, W.S.; Vriesendorp, F.; Pestronk, A.; Caress, J.B.; Katz, J.; Simpson, E.; Rosenfeld, J.; Pascuzzi, R.; Glass, J.; Rezania, K.; Harmatz, J.S.; Schoenfeld, D.; Greenblatt, D.J. Systemic pharmacokinetics and cerebrospinal fluid uptake of intravenous ceftriaxone in patients with amyotrophic lateral sclerosis. J. Clin. Pharmacol. 2014, 54, 1180–1187.
[15]	Akl, M.A.; Ahmed, M.A.; Ramadan, A. Validation of an HPLC-UV method for the determination of ceftriaxone sodium residues on stainless steel surface of pharmaceutical manufacturing equipments. J. Pharm. Biomed. Anal. 2011, 55, 247–252.
[16]	Kauss, T.; Marchivie, M.; Phoeung, T.; Gaubert, A.; Désiré, A.; Tonelli, G.; Boyer, C.; Langlois, M.H.; Cartwright, A.; Gomes, M.; White, N.; Gaudin, K. Preformulation studies of ceftriaxone for pediatric non-parenteral administration as an alternative to existing injectable formulations. Eur. J. Pharm. Sci. 2017, 104, 382–392.
[17]	Harvey, B.; Johnson, T.N.; Yeomanson, D.; Mulla, H.; Mayer, A.P. Ceftriaxone pharmacokinetic properties during continuous veno-veno haemofiltration using an in vitro adult, paediatric and neonatal model. Perfusion. 2014, 29, 32–38.