HPLC determination of serum ganciclovir using ultrafiltration, ultraviolet and fluorescence detection

Koel, Marlies; Nebinger, Peter

doi:10.1016/0731-7085(94)90022-1

Cited by 15 publications

(7 citation statements)

References 7 publications

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“…Ganciclovir determinations were done by high performance liquid chromatography (HPLC) using a previously reported method [24], with the addition of guanosine as an internal standard. Ganciclovir was extracted from plasma by a protein precipitation with acetonitrile, followed by centrifugation and dilution with a mobile phase buffer consisting of 0.05 mM octanesulfonic acid in 100 mM of potassium phosphate containing 3% acetonitrile at a pH of 3.0, and finally injection into the chromatograph.…”

Section: Methodsmentioning

confidence: 99%

Ganciclovir pharmacokinetics and cytokine dynamics in renal transplant recipients with cytomegalovirus infection

Tornatore¹,

Garey²,

Saigal³

et al. 2001

Clinical Transplantation

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Ganciclovir is considered to be the first-line treatment for cytomegalovirus (CMV) in renal transplant recipients. This infection is also associated with elevations of specific plasma cytokines post-transplantation. To investigate daily cytokine response to therapy and ganciclovir pharmacokinetics, 4 transplant recipients (3 males, 1 female) with stable renal allograft function diagnosed with CMV infection were enrolled less than 4 months post-transplant. A creatinine clearance (ClCr) was generated by the Cockroft-Gault (C-G) equation (range: 42.3-68.5 mL/min) to determine ganciclovir dosing. Blood samples were collected for ganciclovir and cytokine [including interleukin (IL)-1beta, IL-2, IL-3, IL-4, IL-6, IL-8, IL-10, TNF-alpha, GM-CSF, and interferon (IFN)-gamma analyses after 7 d of intravenous (i.v.) ganciclovir (dosage range: 165-400 mg daily) therapy and again after 7 d of oral (p.o.) ganciclovir (dosage range: 1000 mg, 2-3 times daily) therapy. Pharmacokinetic ganciclovir was described with a two-compartment model. Total clearance of ganciclovir was consistently greater than ClCr, suggesting tubular secretion. Peak concentrations for i.v. ganciclovir averaged 8.39+/-1.87 microg/mL with minimum concentrations of 0.48+/-0.35 microg/mL. Plasma concentrations were lower but more sustained during a p.o. dosing interval (max=2.12+/-0.58 microg/mL, min=1.15+/-0.34 microg/mL). IL-6, IL-8, IL-10, and TNF-alpha were detectable at multiple times during the study periods while the remainder of the cytokines were only intermittently detectable. Average concentrations (i.v. versus p.o. study period) for TNF-alpha were 40.1+/-17.5 versus 22.1+/-11.2 pg/mL, for IL-8 were 17.1+/-15.6 versus 4.12+/-2.59 pg/mL, and for IL-10 were 7.39+/-5.54 versus 2.64+/-1.06 pg/mL. Concentrations were similar for IL-6 during both studies (9.39+/-5.42 versus 14.7+/-14.8 pg/mL). TNF-alpha, IL-8, and IFN-gamma appeared to correlate with CMV antigenemia. Further investigation of ganciclovir disposition and changes in plasma cytokines in renal transplant recipients during CMV infection may provide insight into variable antiviral responses in renal transplant recipients.

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Section: Methodsmentioning

confidence: 99%

Ganciclovir pharmacokinetics and cytokine dynamics in renal transplant recipients with cytomegalovirus infection

Tornatore¹,

Garey²,

Saigal³

et al. 2001

Clinical Transplantation

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“…Quantification of ganciclovir was achieved by simultaneous ultraviolet (u.v.) at 254 nm, and fluorescence detection (excitation and emission wavelengths at 285 nm and 380 nm, respectively) [19]. This method exhibited linear ranges of 20–1000 ng ml −1 (u.v.)…”

Section: Methodsmentioning

confidence: 99%

Increased oral ganciclovir bioavailability in HIV‐infected patients with chronic diarrhoea and wasting syndrome—a population pharmacokinetic study

Mouly

Aymard

Tillement

et al. 2001

Brit J Clinical Pharma

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Aims Despite a lack of data, the antiviral agent ganciclovir is not indicated in AIDS patients with diarrhoea because of its presumed poor oral bioavailability. To assess the effect of diarrhoea on ganciclovir intestinal absorption, we conducted a pharmacokinetic study in 42 HIV‐infected patients categorized into three groups: A, HIV stage A and B (n = 15); B, AIDS stage C (n = 13); C, AIDS with chronic diarrhoea and wasting syndrome (n = 14). Methods Each patient was evaluated for nutritional (body mass index, albumin, transferrin serum levels), inflammatory (haptoglobin, orosomucoid), immunological (CD4 count, plasma viral load) and intestinal (d‐xylose test, faecal fat and nitrogen output, intestinal permeability) status. Ganciclovir (1 g) was administered orally to fasted patients. Six blood samples were collected over 24 h. Serum was analysed for ganciclovir by h.p.l.c. Population pharmacokinetic analysis was performed using a nonlinear mixed effects modelling program, MP2. Results Mean intestinal permeability (lactulose/mannitol urinary ratio) was increased in group C (0.2) compared with group A (0.05) and B (0.1) patients. Drug concentration‐time profiles were best described by a two‐compartment model. Apparent oral clearance (CL/F) and central volume of distribution (V1/F) were influenced by clinical status (group). For groups A and B combined, final parameter estimates of CL/F and V1/F were 256 ± 98 l h−1 and 1320 ± 470 l, respectively. Final parameter estimates for group C were 118 ± 108 l h−1 and 652 ± 573 l for CL/F and V1/F, respectively. The 95% confidence intervals on differences between A and B combined and C were statistically significant ([ + 70, + 206] for CL/F, and [+ 314, + 1022] for V1/F). Compared with groups A and B, ganciclovir CL/F was significantly decreased in group C patients. Conclusions AIDS patients with diarrhoea and severe disease may benefit from ganciclovir therapy, but a dose adjustment may be required according to their digestive and immunological status.

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“…If protein binding proves to be low, ultrafiltration as a means of deproteinization of the serum samples can be applied. Although ultrafiltration is commonly used for determining free unbound drug levels in serum [21], it has previously been applied as a means of sample preparation for other polar compounds such as acyclovir, ganciclovir, ribavirin and zidovudine [13,[22][23][24][25]. The obtained ultra filtrate is purely aqueous which is particularly suitable for injecting onto LC-systems that are equilibrated under the same conditions.…”

Section: Protein Binding and Ultrafiltrationmentioning

confidence: 99%

Quantification of isoniazid, pyrazinamide and ethambutol in serum using liquid chromatography-tandem mass spectrometry

Sturkenboom¹,

Lijke²,

Jongedijk³

et al. 2015

J Appl Bioanal

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Clinical studies on tuberculosis have shown a correlation between low drug exposure and treatment failure and acquired drug resistance. Objective was to develop a LC-MS/MS method for the quantification of isoniazid, pyrazinamide and ethambutol. Stable isotope-labelled isoniazid-D4 and ethambutol-D4 were used as internal standards. Protein binding of isoniazid, pyrazinamide and ethambutol was investigated and proved low. Therefore, sample preparation using ultrafiltration could be applied, resulting in linear calibration curves in the range of 0.2-8 mg/L for isoniazid and ethambutol and 2-80 mg/L for pyrazinamide. The method was validated according to the guidelines of the FDA. A fast, simple and reliable LC-MS/MS method has been developed for the simultaneous determination of isoniazid, pyrazinamide and ethambutol in human serum for therapeutic drug monitoring and pharmacokinetic studies.

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HPLC determination of serum ganciclovir using ultrafiltration, ultraviolet and fluorescence detection

Cited by 15 publications

References 7 publications

Ganciclovir pharmacokinetics and cytokine dynamics in renal transplant recipients with cytomegalovirus infection

Ganciclovir pharmacokinetics and cytokine dynamics in renal transplant recipients with cytomegalovirus infection

Increased oral ganciclovir bioavailability in HIV‐infected patients with chronic diarrhoea and wasting syndrome—a population pharmacokinetic study

Quantification of isoniazid, pyrazinamide and ethambutol in serum using liquid chromatography-tandem mass spectrometry

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