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PharmacokineticsAmpicillin Ceftriaxone Vancomycin
Half-Life:
1-1.8 hrProtein Bound: 15-25%Absorption: oral 50%Metabolism: hepaticExcretion: urine
Half-Life:
5-9 hrProtein Bound: 85% to 95%Absorption: IM: well absorbedMetabolism: liverExcretion: urine (33%-65%); feces
Half-life:
5-11 hrDistributionwidely in body tissues and fluidProtein Bound: 10-50%Excretion (IV): urine (oral): feces
PharmacokineticsRifampin Meropenem
Absorption: oral well absorbed
Distribution: highly lipophilic; crosses blood-brain barrier well Protein Bound: 80%Half-life 3-4 hrMetabolism: hepatic; undergoes enterohepatic recirculationExcretion: feces (60-65%) and urine (~30%) as unchanged drug
Vd: adults: ~0.3 L/kgDistribution: penetrates
well into most body fluids & tissues; Protein Bound: 2%Metabolism: hepatic Excretion: urine (~25% as inactive metabolites)Half-Life 1-1.5 hr
Pharmacotherapy of meningitisBecause herpes encephalitis can resemble bacterial meningitis at
presentation
acyclovir is usually included with the initial empirical therapy, IV 10-15 mg/kg/dose every 8 hours for 10-14-21 days
Pharmacokinetics• Absorption: oral: 15-30%• Protein Bound: 9-33%• Half-life: 3 hr• Peak Plasma TimeOral: within 1.5-2 hrIV: within 1 hr• Metabolism: hepatic (small amounts)• Excretion: urine (30-90% as unchanged drug)
Pharmacokinetics of dexametasone
• Half-Life: 2-3.5 hr
• Onset: IM: 8-24 hrPeak Plasma Time:
IM: within 8 hr PO: 1-2 hr
• Vd: 2 L/kg• Metabolism: liver• Excretion: mainly in urine,
minimally in bile
Levodopa The main pharmacokinetics parametres
• Peak Plasma Time: 0.5 hr (conventional), 2 hr (XR);• Peak Plasma Concentration: XR is 35% conventional. • Duration 5 hr (short duration improvement), 3-5
days (long duration response). • Vd: levodopa 65% body weight• Protein Bound: 10-30%• Metabolism: hepatic metabolism• Excretion: Urine (80-85%)
Dopamine agonists • Apomorphine. Initial: 2 mg (0.2 mL) SC The main pharmacokinetics parametres • Peak Plasma Time:10-60 min. • Half-life, elimination: 30-60 min.• Vd: 218 L. • Metabolism: hepatic metabolism. • Excretion: Urine (93%); feces (16%).
Dopamine agonists• Pramipexole The main pharmacokinetics parametres• Peak Plasma Time: 2 hr (IR); 6 hr (ER), • Bioavailability: >90%. • Protein Bound: 15%/• Vd: 500 L. • Metabolism <10%. • Half-Life: 8 hr (12 hr in elderly)/• Excretion: urine 90%.
Dopamine agonists
• Ropinirole The main pharmacokinetics parametres• Peak Plasma Time: (Conventional) 1-2 hr; (ER) 6-10
hr. • Bioavailability: 55%.• Protein Bound: 40%. • Half Life: (ER): 6 hr.• Vd: 525L. • Metabolism: Hepatic CYP1A2. • Excretion: Urine.
Dopamine agonists• Rotigotine The main pharmacokinetics parametres• Bioavailability: 37%. • Peak plasma time: 15-18 hr. • Protein Bound: 92% (in vitro); 89.5% (in vivo).• Vd: 84 L/kg. • Metabolism: hepatic. • Half-life, biphasic: 3 hr (initial); 5-7 hr (terminal). • Excretion: 71% urine; 23% feces.
Antiviral drug • Amantadine The usual dosage is 100 mg given twice a day when
used alone. The main pharmacokinetics parametres • Onset: Within 48 hr (antidyskinetic). • Peak plasma time: 2-4 hr. • Half-life elimination: 16 hr (avg; normal renal
function).• Vd: 3-8 L/kg. • Protein Bound: 67%. • Bioavailability: 86-90%. • Metabolism: hepatic• Excretion: Urine (80-90% unchanged)
Anticholinergics• Trihexyphenidyl • Initial: 1 mg PO first day, then increase by 2 mg q3-
5days until reach 6-10 mg/days.• Maintenance: 5-15 mg/day PO divided q6-8hr. The main pharmacokinetics parametres• Half-Life elimination: 33 hr. • Onset: 1 hr. • Peak effects: 1.3 hr. • Duration: 6-12 hr. • Metabolism: Unknown. • Excretion: Urine and bile.
Anticholinergics• Benztropine mesylate 1-2 mg/day (range 0.5-6 mg)
PO/IV/IM qHS OR divided q6-12hr. • Initiate at low doses (0.5-1 mg) qHS and titrate by 0.5
mg q5-6Days.The main pharmacokinetics parameters • Onset of action: 1hr (PO); 15 min (parenteral). • Duration: 6-48 hr. • Protein Bound: 95%.• Bioavailability: 29%.
Anticholinergics• Benztropine mesylate 1-2 mg/day (range 0.5-6 mg)
PO/IV/IM qHS OR divided q6-12hr. • Initiate at low doses (0.5-1 mg) qHS and titrate by 0.5
mg q5-6Days.The main pharmacokinetics parameters • Onset of action: 1hr (PO); 15 min (parenteral). • Duration: 6-48 hr. • Protein Bound: 95%.• Bioavailability: 29%.
MAO-B inhibitors • Selegiline • Conventional 5 mg PO at breakfast & 5 mg at lunch (10 mg/day). Not to
exceed 10 mg/day. • Orally-disintegrating (with levodopa/carbidopa). Initial 1.25 mg PO qDay, may increase after 6 weeks if inadequate
response, no more than 2.5 mg/day. The main pharmacokinetics parameters • Peak plasma time: (conventional) 0.5-0.9 hr; (ODT) 15-40 min. • Half-life elimination: 10 hr (PO); 18-25hr (TD). • Duration: 24-72hr (PO). • Bioavailability: 10%. • Protein Bound: 90%.• Vd: 300 L. • Metabolism: cytochrome P-450 enzymes. • Excretion: Urine.
MAO-B inhibitors• Rasagiline at a dosage of 1 mg once daily is given
as monotherapy. The main pharmacokinetics parameters• Half-Life elimination: 1.3-3 hr.• Peak Plasma Time: 1 hr. • Bioavailability: 36%. • Protein Bound: 88-94%.• Vd: 87 L. • Metabolism: liver, primarily CYP1A2 (in vitro data). • Excretion: Urine (62%); feces (7%).
COMT Inhibitors• Tolcapone The usual dosage is 100-200 mg PO q8hr. Always as an
adjunct to levodopa/carbidopaThe main pharmacokinetics parameters• Peak Plasma Time: 2 hr. • Bioavailability: 65-85%.• Protein Bound: >99.9%. • Half-life elimination: 2-3hr. • Vd: 9 L. • Metabolism: Liver glucuronidation. • Excretion: Urine (60%); feces (40%).
COMT Inhibitors• Entacapone • The usual dosage is 200 mg PO with each dose of
levodopa/carbidopa• Not to exceed 1600 mg/day.The main pharmacokinetics parameters• Peak Plasma Time: 1 hr. • Bioavailability: 35%.• Protein Bound: 98%. • Vd: 20 L. • Half-life elimination: 0.4-0.7 hr (B-phase); 2.4 hr
(Y-phase). • Metabolism: Hepatic glucuronidation. • Excretion: Feces (90); urine (10%).
Nonopioid Analgesics Para-aminophenol derivative
Acetaminophen650–1000 mg q 6–8 h
Pharmacokinetics• Peak Plasma Time:
10-60 min 8 hr (PO 650 mg, extended-release tablet)
• Peak Plasma Concentration: 1.8 -2.1 mcg/mL • Distribution: 1 L/kg• Protein Bound: 10 to 25%
• Metabolism: Liver (microsomal enzyme systems); conjugation (glucuronic/sulfuric acid)
• Half-life elimination: 1.25-3 hr• Excretion: urine
• Time to Peak:Oral: 10-60 minutesIV: 15 minutes
NSAIDThe main pharmacokinetics parameters
of indoles
Diclofenac• Bioavailability: 50-60%• Protein Bound:
99-99.8%
• Vd: 1.3-1.4 L/kg• Metabolism: liver
(hydroxylation and conjugation with glucuronic acid, taurine amide, sulfuric acid)
• Half-life: 1.2-2 hr• Excretion:
urine 50-70% feces 30-35%
Indomethacin• Bioavailability: 100%• Onset: 30 min• Duration: 4-6 hr• Protein Bound: 99%• Vd: 0.34-1.57 L/kg• Metabolism: Liver• Half-life:
1 hr (initial phase); 2.6-11.2 hr (2 phase)
• Excretion: urine 60%
feces >33%
NSAIDThe main pharmacokinetics parameters
Nabumetone• Onset: Several days
• Protein Bound: >99%
• Vd: 29-82L • Metabolism: Hepatic
• Half-life elimination: 24 hr
• Excretion: urine (80%)
feces (9%)
Piroxicam• Half-life:14-158 hr (average
50 hr)
• Onset: 15-30 min -1 hr
• Duration: 48-72 hr• Protein Bound: 99.3%• Vd: 0.12-0.14 L/kg• Metabolism: hydroxylation;
conjugation by cyclodehydration
• Excretion: urine, feces
NSAIDThe main pharmacokinetics parameters
• e
Ibuprofen Ketoprofen Naproxen
Half-life 2-4 hr 2-4 hr
Onset 30-60 min <30 1 hr
Duration 4-6 hr 6 hr 4-7 hr
Vd 0.12 L/kg 0.1 L/kg 0.16 L/kg
Protein Bound 90-99% 99% <99%
Bioavailability
80-100% 90% 95%
Metabolism Rapid hepatic oxidation
hepatic hepatic conjugation
Excretion Urine 50-60% (<10% unchanged)
Urine 50-90% feces 1-8%
Urine 95%; feces <5%
NSAIDThe main pharmacokinetics parameters
• e
Aspirin Meclofenamate
Half-life 2-3 hr (low dose); 15-30 hr (higher dose)
40 min-5.3 hr
Onset PO 5-30 min; PR 1-2 hr 30 min
Duration PO 3-6 hr PR >7 hr
Vd 0.15-0.2 L/kg
Protein Bound
90-95% 99.8%
Bioavailability
80-100% 26%
Metabolism Hepatic via microsomal enzyme system
Hepatic
Excretion principally in urine (80-
100%), saliva, feces urine (70%); feces (20-30%)
Opioid Analgesics The main pharmacokinetics parameters
Phenylbutazone
Ketorolac Celecoxib
Half-life 60 hr 2-6 hr 11 hr
Onset IM: 10 min; PO: 30-60 min
Duration 6-8 hr
Vd 0.11-0.33 L/kg 7.14 L/kg
Protein Bound
98% >99% 97%
Bioavailability
80-100% undetermined
Metabolism hepatic hepatic hepatic (CYP2C9)
Excretion urine Urine (91%); feces
feces 57%; urine 27%
Opioid Analgesics The main pharmacokinetics parameters
Codeine Hydrocodone Propoxyphene Half-life: 3-5 hrOnset: RapidDuration: 2-4 hr (SC/IM)Peak Plasma Time: SC 40-60 min; IM 30-50 minBioavailability: 50-60%; Protein Bound: 60-80%Metabolism: liver Excretion: urine (primarily)
Half-life: 3.3-4.4 hrDuration: 4-8 hrPeak Plasma Time: 1.3 hr (single 10 mg dose)Concentration: 23.6 ng/ml (single 10 mg dose)Metabolism: liver
Excretion: urine
(mainly)
Half-life: 6-12 hrDuration: 4-6 hrPeak Plasma Time: 2-2.5 hrConcentration: 50-120 ng/mLMetabolism: prolonged, hepaticExcretion: urine (primarily)
Opioid Analgesics The main pharmacokinetics parameters
Fentanyl Levorphanol
Half-life 2-4 hr 12-16 hr
Onset immediate (IV)7-15 min (IM)
10-60 min (PO)
Duration 1-2hr (IM); 0.5-1hr (IV)
4-8 hr
Vd
Protein Bound 80-85%
Bioavailability
50%
Metabolism hepatic hepatic
Excretion urine (75%), feces urine
Opioid Analgesics The main pharmacokinetics parameters
Meperidine
Methadone
Morphine
Half-life 0.5-1 hr 8-59 hr 1.5-4.5 hr
Onset 30-60 min (PO); 10-30 min (IM)
0.5-1 hr (oral); 10-20 min (parenteral)
15-30 min (PO); <5 min (IV)
Duration 4-6 hr 4-6 hr up to 7 hr
Vd 3.5 L/kg (PO); 2.6 L/kg (IM)
1-4.7 L/kg (IV)
Protein Bound
25% 85-90% 36% (IV)
Bioavailability
36-100%
Metabolism liver liver liver
Excretion urine, feces urine urine & feces