PHARMA LAB SGD DRUG PK PRESENTATIONS

Group 1-A1
Description: Etoricoxib, an NSAID, is a selective cyclo-oxygenase-2 (COX-2)
inhibitor. Its anti-inflammatory and analgesic action is exhibited by inhibition of
prostaglandin synthesis via inhibition of COX-2.
Pharmacokinetics:
Absorption: Well absorbed from the gastrointestinal tract, food delays rate of
absorption. Absolute bioavailability: Approx 100%. Time to peak plasma
concentrations: Approx 1 hour (without food), 2 hours (with food).
Distribution: Volume of distribution: 120 L. Plasma protein binding: Approx
92%.
Metabolism: Extensively metabolised via CYP3A4 isoenzyme to form 6’-
hydroxymethyl derivative of etoricoxib, then oxidised to 6’-carboxylic acid
derivative (major metabolite).
Excretion: Mainly via urine (70%), 20% in faeces, <2% as unchanged drug.
Elimination half-life: Approx 22 hours

Group 2-A1
Enalapril maleate
* is an orally active angiotensin-converting enzyme inhibitor.
* It lowers peripheral vascular resistance without causing an increase in
heart rate.
* Most patients achieve adequate blood pressure control on enalapril
alone or with hydrochlorothiazide.
* In patients with severe congestive heart failure resistant to
conventional therapy, enalapril improves cardiac performance by a
reduction in both preload and afterload, and improves clinical status
long term.

Liberation

Absorption of enalapril
*Oral enalapril is rapidly absorbed with peak serum concentration
occuring within 1 hour
* it has an oral bioavailability of 60%
* absorption of oral enalapril is not influenced by the presence of food in
the GIT
*rapidly and extensively hydrolysed to enalaprilat - a potent angiotensin
converting enzyme inhibitor
*peak serum concentration of enalaprilat occur 3 to 4 hours after an oral
dose of enalapril
*effective half-life for accumulation of enalaprilat followoing multiple
doses of enalapril is 11 hours
*subject with normal renal function, steady state sreum concentrations
of enalaprilat were achieved by the 4th day of treatment

Topic: distribution
#Following administration of enalapril,there is an increase in renal
BLOOD FLOW ;decreases renal vascular resistance,thus it reduces
blood pressure in hyper tensive patients.
# the volume of distribution of enalapril has not been established.As a
pro drug ,enalapril is converted by de- esteriifcation into enalaprilat.It is
shown to penetrate into most tissues in particular the kidneys and
vascular tissue although penetration of blood brain barrier has not been
demonstrated aftr administration at therapeutic doses .
#minimal penetration occurs into breast milk but significant fetal transfer
occurs.
# it is reported that less than 50% of enalaprilat is bound to human
plasma proteins,based in limited data from binding studies of enalaprilat
in human plasma both by equilibrium dialysis and by ultrafiltration.

Metabolism
https://proteopedia.org/wiki/index.php/Enalapril
-Enalapril is quickly metabolized into Enalaprilat, the more active
metabolite, by the hepatic enzyme CYP3A4.
-https://www.drugbank.ca/drugs/DB00584
About 60% of absorbed dose is extensively hydrolyzed to Enalaprilat via
de-esterification mediated by hepatic esterases.

Metabolism( Sah)
About 60% of the absorbed dose is extensively hydrolyzed to enalaprilat
via de-esterification mediated by hepatic esterases.Label In humans,
metabolism beyond bioactivation to enalaprilat is not observed.5

Elimination
Source: Medscape>Drugs>Pharmacology
Half-life elimination is 2 hours (parent drug), 35-38 hours for enalaprilat,
its active metabolite. It can also be removed by dialysis. It is excreted by
urine (61%) and feces (6% as enalapril, 27% as enalaprilat)

Response
- The active metabolite of enalapril competitively inhibits the ACE to
hinder the production of angiotensin II, a key component of the renin-
angiotensin-aldosterone system that promotes vasoconstriction and
renal reabsorption of sodium ions in the kidneys. Ultimately, enalaprilat
works to reduce blood pressure and blood fluid volume.
Group 3-A1
Aspirin (ACETYLSALICYLIC ACID)

MIMS Classification
Non- steroidal anti-inflammatory drug
Mechanism of Action
Inhibits synthesis of prostaglandin by cyclooxygenase; inhibits platelet
aggregation; has antipyretic and analgesic activity
Liberation
Oral, rectal, lysine acetylsalicylate may be given intravenously or
intramuscularly
Absorption
Bioavailability: 80-100%
Onset: PO, 5-30 min; PR, 1-2 hr
Duration: PO, 4-6 hr; PR, >7 hr
Peak plasma time: PO, 0.25-3 hr
Peak plasma concentration: Analgesia/antipyresis, 30-100 mcg/mL;
anti-inflammatory, 150-300 mcg/mL
Distribution
Protein bound: ≤100 mcg/mL, 90-95%; 100-400 mcg/mL, 70-85%;
higher concentrations, 25-60%
Vd: 170 mL/kg (150-200mL/kg)
Metabolism
Metabolized by liver via microsomal enzyme system
Metabolites: Salicylurate, salicyl phenolic glucuronide, salicyl acyl
glucuronide, 2,5-dihydroxybenzoic acid (gentisic acid), 2,3-
dihydroxybenzoic acid, 2,3,5-trihydroxybenzoic acid, gentisuric acid
(active)
Enzymes inhibited: Cyclooxygenase (insignificant)

Elimination
Half-life: Low dose, 2-3 hr; higher dose, 15-30 hr
Renal clearance: 80-100% in 24-72 hr
Excretion: Urine (80-100%), sweat, saliva, feces
Dialyzable: Yes

GROUP 4- A1 CEFUROXIME
Group 6- Ibupofen
Group 7- Enalapril
Description: Enalapril, a prodrug of enalaprilat, competitively inhibits ACE from
converting angiotensin I to angiotensin II (a potent vasoconstrictor) resulting in
increased plasma renin activity and reduced aldosterone (a hormone that
causes water and Na retention) secretion. This promotes vasodilation and BP
reduction.
Onset: Approx 1 hr.
Duration: 12-24 hr.
Pharmacokinetics:
Absorption: Well absorbed from the GI tract (approx 60%). Time to peak
plasma concentration: Oral: Enalapril: Approx 1 hr; enalaprilat: 3-4 hr.
Distribution: Distributed into milk (trace amounts), crosses the placenta and
appears to cross the blood-brain barrier poorly. Plasma protein binding:
50-60% (enalaprilat).
Metabolism: Extensively hydrolysed to enalaprilat in the liver via esterases.
Excretion: Via urine (43% as enalaprilat and 18% as enalapril); faeces (27%
as enalaprilat and 6% as enalapril). Elimination half-life: Approx 11 hr.
Group 9 -A2

Group 10 Sec A2

Drug: Albendazole
Description: Albendazole, benzimidazole derivative, is an antihelminthic that
inhibits microtubule formation by binding to colchicine sensitive site of beta-
tubulin resulting to decrease in microtubules leading to decline in glucose
uptake and absorptive function and depletion of glycogen storage by adult and
larval forms of parasites. Insufficient glucose causes lack of ATP resulting to
death of parasite.

Pharmacokinetics
Absorption: Poorly absorbed from the GI tract. Absorption may be enhanced by
a fatty meal. Time to peak plasma concentration: 2-5 hr.
Distribution: Widely distributed throughout the body including the bile and CSF.
Plasma protein binding: approximately 70%.
Metabolism: Undergoes extensive hepatic first-pass metabolism, converting to
albendazole sulfoxide.
Excretion: Mainly via the bile and small amounts in urine. Plasma half-life:
approximately 8.5 hr