Universiteit van die Oranje-Vrystaat - SAMJ Archive Browser

622 SAW VOL. 80 7 DES 1991
BEPALING VAN KAFEiEN IN URIEN EN
PLASMA DEUR GASCHROMATOGRAFIE
H&KEu&K en PJ van der Merwe
Dept Farmakologie, UOVS BLOEMFONTEIN
Inleiding
Kafeien, 'nstimulant vandie sentrale senuw&lsel, word soms inge-
neem om sportprestasies te verbeter. Gevolglik beskou die Interna-
side Olimpiese Komitee dit as 'n oortreding as die konsentrasie~n
kafeb in urien her as l&@ is. Om dus MS te stel watter kafeien-
konsentrasie bereik word na die inname van kafeien, is dit noodsaaklik
om 'n betroubare metode te h€ om kafeien te be@ in biologiese
vloeistawwe.
Doe1
Die doe1 van die studie was dus om 'n vinnige, eemudige ea betrou-
bare metode te ontwikkel vir die bepaling van kafeien in plasm en
urien, deur gebruik te maak van gaschromatografie.
Metade
Plasma- of urienmomters (lml), met metakaloon as inteme standaard,
is g&kstraheer met tolueen:chlor&rm en die organiese fase is op die
gaschr~~tograaf~~~espuit
Rewltate
Die kalibrasiekromme van kafeien in urien en plasma is hie& tot
35/(g/ml Die laagste akkuraat-bepaalbare konse&asie van kafeien in
urien en plasma is onderskeidelik 0,2 en l,@g/ml
Gevolgimkking
Met hierdie analitiese metode kan kafe'ienkonsentrasies in urien en
plasma op 'n betroubare, eemudige en vinnige metode bepad word.
Tegelykertyd kan ook vasgestel word of die maksimum toelaatbare
kafeienkonsentrasie van l&@ in urien nie oonkry word nie.
cMX-4ms
THE INFLUENCE OF BENZBROMARONE, AS IN
ALLOMAUON~, ON ALLOPURINOUOXUP~IUNOL KINETICS
IN PATIENTS WITH GOUT
F0 Miiller, G Groenewoud, HKLHundt, R Schall, JCvan der Merwe,
M van Dyk. Department of -, University of the Orange
Free State, BLOEMFONTEIN, South Africa
Gout is characterised by either excessive productionor decreased renal
clearance of uric acid or both of these. Therefore. wevention of
attadrs of acute gout & based on decreasing produdon (xanthine
axidase inhibitors) and enhancing excretion (uricosuric agents) of uric
acid Following absorption, themthine oxidase inhibitor, allopurinol,
is rapidly converted to its active metabolite, oxypurinol, which has a
half-Iife of 18 to 30h. The slow renal clearance of axypurinol, apparently
due to tubular reabsorption, suggests that its elimination may be
enhanced by uricosuric agents like benzbromarone.
The objective of this study wasdo establish if, and to what extent,
benzbromarone. as in Allomaron (allo~urinol lOOme + benzbromarone
20mg), allopurino~&urinbl *tics an2 to compare the
uric acid lowerine ca~abiiities of Allomaron and allo~urinol alone in
patients with co&r~&~I gout.
Fourteen adult males participated in this open, randomised, cross-over
studv. All ~atients had been on allo~urinol as sole maintenance therapy.-Mte;a
7 day run-in period witk 2fMmg allopurinol @yloprimK)
mane, patients we% randomly allocated to AUomaron (2 tablets
mane) or Zyloprim (200mg mane). Eight days later cross-over was
effected and the alternate treatment instituted for a further 7 days. On
days 7 and 14 the subjects were hospitalised and venous blood samples
obtained over a 24h period for allopurinol and axypurinol assays by
means of an HPLC method. Serum uric acid was determined on days
-14,l. 7 and 14.
-administration of allouurinol and benzbromarone resulted in a
signiscant reduction in piasma oxypurinol concentrations, probably
due to comtitive inhiition of renal tubular reabsorption of oxypurino1
by be&omarone. In spite of this obsewed pharmacol&etic
interae'tion the combination of allopuripol and benzbromarone
(U)Omgl40mg daily) is significantly &re effective than allopurinot
(200mg daily) alone in lowering serum uric acid concentrations.
THE PHARMACOKINETICS OF MIGLXTOL OVER A
THERAPEUTIC DOSE RANGE'
~~~~~iiller,~vanq.k,~~~;uug~~ro
Hundt. Dept of Pharmacology, UOFS, PO Box 339, Bloemfontein.
The therapeutic principle of glueosidase hhiition is a valuable advance
in the improvement of metabolic ward h diabetic patients.
Miglitol (BAY m IOW), a potent and safe intestinal alpha-glueosidase
inhibitor, prevents post-prandial blood-glucose and -insulin peaking
after a carbohydrate-rich meaZ
The purpose of the study was to determine the pharmacokinetic variables
of miglitol wer the dose range of 25- 50mg lOOmg and 200mg.
A double-blind, cross-over study was employed The treatment phases
were semted bv a 7 &vs drue-free interval. Blood (0-10hl and urine
(&24hjsamPles kere &11ecte'd for migliml assays.' ~6tio11 was
adnhktered at the beginning of a standard breakfast Twenty-five
healthy, non-smoking male subje.cts, aged between 18 and 23 years,
completed all the treatment phases. Miglitol was determined in p b
after de~roteinisation fultrafiltration\ and in mine after a~~ro~riate
dilution'by measuring 'the inhibition capacity against a-gf~~dasc.
P-nitrophenyl-a-D-gluc~~ranoside (NPG) was used as substrate.'Ibe
p-nitrophe&l reld &ring the eq&tic reaction semd as a
measure of the inhibited and non-inhiibited enzyme reactions.
Miglitol does not obey linea~ kinetic principles. The normalised Crnar
(W) decreased (242 1.90.1.45 and 1.02\. tmax Ih\ increased (2.12
-,-275 and 331) &d t6e normalised'hJ~ (&W) decrd
(11.9, 11.0.858. and 7.28). The terminal half-life (h) increased (2.16.
%23,236 and 2W) and& percentage urinary ;e;?overy decreased
(95.7,90.1,755 and 59.7) as the dose of midito1 was increased over the
&ge 25mg, SOq, 100& and 200mg reqkctively.
Miglitol absorption and elimination kinetics are not linear: '"Satura-
tion" of absomtion Drocesses aDDears to occur with inmeasinn oral
doses. ~urtherbore,ihe eliminalibn half-life increased as a funzon of
dose. Cumulation must therefore be considered a ~~sslbilihr with
multiple dosing in the 200mg or higher range. The auence hf impaired
renal function on miglitol clearance may be of clinical import-
-
ance and needs further investigation.
'n EKSTaAKSIE METODEVIIt DIE GASCHROMATOGRAFIESE
BEPALING VAN 'a YERSKEIDENHEID BASIESE GENEES
MXDDELS IN BXOLOGIESE VLOEISTOWWE
IiKL. Hundt Dept Farmako1ogie. UOVS,
BLOEMFONIEIN
Die ontwikkeling van 'n bepkgmetode wat gebruik maak van 'n
kleinvohune finale ekstrak en geskik is vir die ekstraksie en kwantita-
tiewe bepaling van 'n verskeidenheid basiese geneesmiddels in
biologiese vloeistowwe.
Motode
Die metode behels die ekstraksie met 'n organiese oplosmiddel van
die basiese middel by 'n &skikte pH uit 'n biologiese v1oeistof gevolg
dew terugeJistralrsK in 'mwrduude suuroplossing, aElralinisering van
die suur en 'pfinale ekstmksiein'nkleinvolurne oplosmiddel, wadEvao
$1 gaschromatografies geanaliseer word
Rcsllltate
Genees- Reikwydte Limiet Her- Akknmatheid Presisie
mwel (nghnl) (n%ml) winniag (sylligheid96) (m)
(96) Lae H& h e HOE
h irons Irons Irons
Dotiapien
mew A 1.28-81.0
Dotiapien
0.90
L
59.4 +5.76 -0.U 7.05 156
metode B 1.20-783 1.00 72.7 +7.08 +5.81 4.94 2.23
Chloorfen$amien
121-40.7 1.20 63.7 -1030 -053 22.3 7.27
Dekstrometorfaan
123-20.4 1-00 583 -28.20 + 121 15.8 5.43
~ie
&to& is &kik vir die kwantitatiewe bepaling van 'n versleiden-
heid basiese eeneesmiddek Voldoende henuinnine herhaalbaarheid.