RESUMO
Pharmacokinetics [PK] variation of drugs in males and females may affect therapeutic effectiveness and safety. In current study the PK differences for omeprazole and its metabolites5-hydroxy-omeprazole and omeprazole-sulphone were evaluated in males and females. The current study also considered PK comparison of Pakistani subjects using the CYP2C19 genotype as variable. A single oral dose [40mg omeprazole], open-labeland, non-controlled clinical trial was arranged. Samples were quantified using reversed phase HPLC-UV method. CYP2C19 genotype of subjects was determined by tetra primer polymerization chain reaction [PCR] assay. There was a significant increase in Cmax [from 2 to 2.9microg/ml, p=0.004], [from 6.67 to 8.74microg-hr/ml, p=0.05] and elimination half-life [from 1.05 to 2.1 hr, p=0.0001] of omeprazole in females compared with males. Cmax and of 5-hydroxy-omeprazole [0.0248 and 0.0001, respectively] and omeprazole-sulphone [0.0001 and 0.001, respectively] was significantly higher in females than males when compared at 95 onfidence interval. The Cmax and AUC of omeprazole showed a significant raise [p=0.01 and 0.04, respectively] in Homz PMs [Homozygous Poor Metabolizers] compared with Homz EMs [Homozygous Extensive Metabolizers] and Htrz PMs [Heterozygous Poor Metabolizers] while Cmax and AUC of 5-hydroxy-omeprazolewas significantly higher [p=0.01 and 0.04, respectively] in Homz EMs compared with Homz PMs and HtrzPMs. AUC of omeprazole was significantly higher in females while its elimination also took longer compared with males. AUC of omeprazole was significantly higher in Homz PMs indicating that CYP2C19 displayed genetically deficient metabolism in its homozygous state
RESUMO
The haemodynamic changes encountered in spinal anaesthesia are directly related to the extent of sympathetic block and can be decreased by restricting the block to unilateral sympathetic chain. This prospective quasi experimental study compared the changes in heart rate and blood pressure in unilateral and bilateral spinal anaesthesia to demonstrate that unilateral block caused less haemodynamic changes. Sixty ASA I or II patients aged 20 - 60 years for elective inguinal herniorrhaphy were randomly divided into two groups: group - A [unilateral] and group - B [bilateral]; each having 30 patients. Hyperbaric bupivacaine [15 mg] was injected intrathecally in lateral position. Group A patients were kept in lateral position with surgical side down for 10 minutes. In group B, patient's position was immediately changed to supine. Blood pressure and heart rate were recorded prior to and at every 5 - minute intervals after spinal anaesthesia for a duration of 30 minutes. Chi-square and t-test were applied. Frequency of hypotension was 6.7% in group A and 60% in group B [p = 0.00]. Frequency of bradycardia was 6.7% in group A vs. 10% in group B [p = 0.50] while the frequency of tachycardia was 3.3% in group A and 16% in group B [p = 0.09]. Frequency of hypotension was significantly less in unilateral as compared to bilateral spinal anaesthesia