Once-daily dose regimen of ribavirin is interchangeable with a twice-daily dose regimen: randomized open clinical trial

Figures & data

Figure 1 Flow diagram showing the design of the RIBADOS study, with the number of patients included and reasons for discontinuation of intervention.

Figure 2 LC-MS/MS RBV analysis in blood plasma.

Notes: (A) and (B) show the MS spectrum of RBV and the IS, 5-methylcytidine, respectively. (C) Chromatogram of a blank sample with the IS (upper trace). The lower trace shows a typical study sample with RBV. *RBV was detected using precursor ion m/z 245.1 (unit resolution) and product ion m/z 113.1 (wide resolution) at a fragmentation voltage of 80 V and a collision energy of 5 V.
Abbreviations: CID, collision-induced dissociation; ESI, electrospray ionization; frag, fragmentation; IS, internal standard; LC-MS/MS, liquid chromatography-tandem mass spectrometry; Mol, molecular; MRM, multiple reaction monitoring; RBV, ribavirin; wt, weight.

Table 1 Patient characteristics and hematological parameters at the start of the treatment

Sex (male/female)	7/1
Age, years (range)	45 (26–67)
Ethnicity (Caucasian)	8 of 8
High viral load (>800,000 IU/mL)	5 of 8
Aspartate transaminase (range)	69.8 (27–154) U/L
Alanine transaminase (range)	123 (32–369) U/L
Gamma-glutamyl transferase (range)	69.6 (24–137) U/L
Serum creatinine (SD)	89 (9.2) µmol/L
Albumin (range)	40.3 (35.8–44.6) g/L
Liver biopsy (6/8)	F0-1 (3), F2-3 (3)
Metavir classification	Active chronic inflammation

Figure 3 Typical pharmacokinetic profile for RBV in one patient. The first blood sample was taken before intake of the prescribed dose of RBV. The intake is at time zero. In the twice-daily dose regimen, the RBV plasma concentrations were monitored for 12 hours (solid line). In the once-daily dose regimen, the RBV plasma concentrations were monitored for 24 hours (dashed line).

Abbreviation: RBV, ribavirin.

Figure 4 Pharmacokinetic parameters for RBV.

Notes: (A) For each dose regimen, the minimum plasma concentration of RBV during one dose interval was determined. The line connects the data from each patient. (B) Maximum plasma concentration of RBV that is reached within one dose interval for the specified dose regimen. The line connects the data for each patient. (C) AUC of RBV for each dose regimen for the patients. The line connects the data from each patient.
Abbreviations: AUC, area under the concentration-time curve; C_max, maximum concentration; C_min, minimum concentration; RBV, ribavirin.

Table 2 Change in hematological parameters after 4 weeks of treatment

Parameter	1×1,200 mg (n=3)	2×600 mg (n=5)
Hemoglobin (range)	11.8% (3.9 to 18.2)	13.4% (7.7 to 17.8)
Leucocytes (range)	21.4% (0 to 58.6)	51.4% (27.9 to 71.1)
Thrombocytes (range)	13.0% (−27.1 to −47.9)	24.4% (2.4 to 50.6)
Creatinine (range)	0.7% (−10.7 to −8.7)	7.5% (−8.5 to −16.9)

Notes: Hematological parameters at the start of treatment were compared with levels at week 4 after start of treatment. The change is represented as percentage decrease compared with week 0.