INFLUENCE OF CIMETIDINE ON THE PHARMACOKINETICS OF PARACETAMOL IN HEALTHY SUBJECTS
INFLUENCE OF CIMETIDINE ON THE PHARMACOKINETICS OF PARACETAMOL IN HEALTHY SUBJECTS
| dc.contributor.author | BALA, HINA AHMED | |
| dc.date.accessioned | 2014-02-13T09:30:25Z | |
| dc.date.available | 2014-02-13T09:30:25Z | |
| dc.date.issued | 1998-08 | |
| dc.description | A THESIS SUBMITTED TO THE POSTGRADUATE SCHOOL, AHMADU BELLO UNIVERSITY, IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD OF MASTER OF SCIENCE DEPARTMENT OF PHARMACEUTICAL AND MEDICINAL CHEMISTRY FACULTY OF PHARMACEUTICAL SCIENCES AHMADU BELLO UNIVERSITY ZARIA, NIGERIA | en_US |
| dc.description.abstract | Considering the prevalence of peptic ulcer diseases in Nigeria and the popularity of paracetamol as an "household" analgesic, there is the possibility of patients being treated for peptic ulcer to take paracetamol. It is therefore possible for the drug(s) used in the peptic ulcer treatment to influence the pharmacokinetic parameters of paracetamol. The influence of cimetidine (400mg) on the pharmacokinetics of oral single dose (1g) paracetamol was studied in 8 healthy subjects under two protocols (concomitant and delayed paracetamol administration 1 hour after cimetidine). The study was carried out in 3 phases: paracetamol alone (control); paracetamol and cimetidine concomitantly; and paracetamol 1 hour after cimetidine. A wash-out period of 2 weeks was allowed between the phases of the study. The method of residuals was used to obtain the pharmacokinetic parameters using the salivary concentration-time curves generated from the salivary concentration-time data as preliminary data. Statistical analysis was done by the student two-tailed t-test of paired data. Following the single oral one gram dose of paracetamol, the relevant mean pharmacokinetics parameters obtained were in agreement with those in the established literature. For the influence of cimetidine on paracetamol, there were no significant changes (P<0.10) when compared to the control in the salivary pharmacokinetics of paracetamol when the two drugs were concomitantly administered. Delayed administration of paracetamol 1 hour after cimctidine, on the other hand, was associated with significant changes in the pharmacokinetic parameters. The peak salivary concentration (Cmax) and absorption rate constant (Kab) were significantly reduced (P<0.05), while the time to peak concentration (Tmax), absorption half-life (t1/2ab) and lag time were all significantly increased (P<0.05). Elimination half life (t1/2el) and area under the curve (AUC o - oc) were significantly increased (P<0.05 and 0.10 respectively). Elimination rate constant (Kel) and clearance (C1) were significantly reduced (P<0.05 and 0.10 respectively). While Volume of distribution (Vd) was significantly increased (P<0.05). These findings indicated that cimetidine does not affect the pharmacokinetics of paracetamol when the two drugs were concomitantly administered but impaired the absorption and inhibited the metabolism of paracetamol when the administration of the latter was delayed by 1 hour after cimetidine. The therapeutic implications of this interaction is that the efficacy of paracetamol may be affected when the two drugs arc used in combination. | en_US |
| dc.identifier.uri | http://hdl.handle.net/123456789/1344 | |
| dc.language.iso | en | en_US |
| dc.subject | INFLUENCE, | en_US |
| dc.subject | CIMETIDINE, | en_US |
| dc.subject | PHARMACOKINETICS, | en_US |
| dc.subject | PARACETAMOL, | en_US |
| dc.subject | HEALTHY SUBJECTS. | en_US |
| dc.title | INFLUENCE OF CIMETIDINE ON THE PHARMACOKINETICS OF PARACETAMOL IN HEALTHY SUBJECTS | en_US |
| dc.type | Thesis | en_US |