4-aminobenzoic acid

PABA/Drug Interactions:

  • AnestheticsAnesthetics: According to in vitro studies, butyl aminobenzoate (BAB) suspension may elicit long-lasting sensory (nonmotor) blockade when injected epidurally in patients with intractable pain (72; 161; 162). The safety of its use in combination with other anesthetic agents has not been well studied.
  • AntacidsAntacids: Since cimetidine affects intraduodenal pH and trypsin activity, cimetidine may increase PABA absorption and therefore may influence test results relying on measurement of urinary excretion of PABA (163). According to a human study of eight patients undergoing the PABA test for pancreatic insufficiency, PABA test results may rise by approximately 25-30% following administration of cimetidine.
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: According to study in mice, intravenous administration of PABA may have anticoagulant activity (74; 119).
  • Antidiabetic agentsAntidiabetic agents: According to case reports, PABA may cause hypoglycemia (118).
  • AntifolatesAntifolates: According to a review, dihydropteroate synthase (DHPS) inhibitors are sulfur-based drugs that compete at DGPS active sites with para-aminobenzoic acid (164).
  • AntihistaminesAntihistamines: According to case reports, there may be cross-sensitivity between PABA and certain antihistamines, with worsening rash and possible development of autoimmunity in those patients exposed (148).
  • Anti-inflammatoriesAnti-inflammatories: According to animal research, PABA may have anti-inflammatory effects (75). However, PABA's interaction with other anti-inflammatory agents has yet to be determined.
  • AntineoplasticsAntineoplastics: According to an animal study, administration of PABA delayed tumor induction in ultraviolet B irradiated mice (75). It is unclear how PABA may interact with other anti-tumor agents.
  • AntiviralsAntivirals: In human research, PABA appeared to exhibit antiviral synergistic effects when used with other medications, such as acyclovir, in the treatment of herpetic keratitis (53).
  • BronchodilatorsBronchodilators: According to a human study, PAMBA (para-aminomethylbenzoic acid) has been shown to reduce airway hyper-responsiveness following bronchoprovocation challenge in asthmatics (64). It is possible that it may act synergistically with other asthma medications, although there is no evidence to substantiate this hypothesis.
  • CortisoneCortisone: According to anecdotal evidence, oral PABA may increase the effects and side effects of cortisone by decreasing its metabolism (165). Based on one small equivalence trial, PAMBA (para-aminomethylbenzoic acid) given intramuscularly to patients with pemphigus vulgaris may help minimize steroid requirements in these patients (58).
  • Cytotoxic agentsCytotoxic agents: Anecdotal evidence exists regarding PABA's ability to sensitize tumor cells to chemotherapy and radiation. One in vitro study also found that treatment of cells with para-aminobenzoic acid may reduce DNA breakage induced by chemical mutagens (82).
  • DapsoneDapsone: This agent functions as a competitive antagonist of PABA, preventing its utilization by bacteria in the synthesis of folic acid. For this reason, in theory, co-administration of PABA may inhibit the antimicrobial effect of dapsone.
  • Dermatologic agentsDermatologic agents: Photocontact and contact sensitization (increased sensitivity of a patient's skin to light and chemicals) from PABA (115; 116; 117; 1; 149; 150; 136; 141; 147) and contact and photocontact dermatitis due to topical PABA derivatives (134; 16; 151; 138; 150) have been reported. Human research has also reported pruritus with use of PABA taken by mouth daily (65; 125).
  • Digestive enzymesDigestive enzymes: According to a case series, supplemental pancreatic enzymes may increase PABA absorption and recovery in patients undergoing the PABA test for pancreatic insufficiency (13).
  • EstradiolEstradiol: According to a case study, padimate O (octyl dimethyl PABA) may function as a dermal penetration enhancer for systemic delivery of a topical estradiol spray (166).
  • Fibrotic disease agentsFibrotic disease agents: According to an in vitro study, PABA may dose dependently inhibit fibroblast proliferation and glycosaminoglycan secretion (167; 168).
  • Gastrointestinal agentsGastrointestinal agents: Gastrointestinal upset (57; 65; 124) including nausea and anorexia (125) from use of PABA has been reported in human research.
  • Gastrokinetic agentsGastrokinetic agents: According to a case series study, gastrokinetic agents, such as domperidone, may correct for delayed gastric emptying in patients undergoing the PABA test for pancreatic insufficiency (169).
  • Genitourinary agentsGenitourinary agents: In human research, withdrawals from study medication were reported due to adverse events that included irritative symptoms (including urgency, frequency, or pain on urination) and hematuria with an intravesical instillation of PAMBA and bacillus Calmette-Guerin (120).
  • HematologicsHematologics: There have been several reports of methemoglobinemia (a condition in which ferrous iron [Fe2+] in hemoglobin gets oxidized to the ferric state [Fe3+], which results in altered oxygen affinity and impaired oxygen delivery to tissues) caused by topical or local anesthetics containing PABA derivatives (155; 156; 157). Transient leukopenia, particularly upon initiation of PABA treatment, has been noted in U.S. Pharmacopeia reports in 1999.
  • HepatotoxinsHepatotoxins: Jaundice (121) and abnormalities of liver function tests (122) have been noted in patients taking PABA, and hepatotoxicity has been reported from KPAB (potassium para-aminobenzoate) (118).
  • Hormonal agentsHormonal agents: According to a case study, padimate O (octyl dimethyl PABA) may function as a dermal penetration enhancer for systemic delivery of a topical estradiol spray (166).
  • ImmunomodulatorsImmunomodulators: In patients with sensitivity to PABA, continued exposure to it may result in development of autoimmune diseases such as dermatomyositis and systemic lupus erythematosis, according to some case reports (148). Other human research has reported dropouts due to adverse events from PABA including fevers, chills, and cold sweats (65; 125; 120).
  • InterferonInterferon: According to in vitro and in vivo studies, PABA may induce interferon (alpha/beta) production (170).
  • MethotrexateMethotrexate: PABA may interfere with the effectiveness of methotrexate by promoting folic acid synthesis, a pathway that methotrexate inhibits (theoretical).
  • Neurologic agentsNeurologic agents: In human research, headaches from use of KPAB (57), and confusion, anxiety, and concentration difficulty from use of PABA (125) have been reported.
  • Para-phenylenediaminePara-phenylenediamine: Also known as PPD, this molecule has historically been a component of hair dyes. Its structural similarity to PABA has caused allergic reactions due to cross-sensitivity in some patients using PPD-containing hair dyes and/or PABA-containing sunscreens, according to some case reports (148).
  • Photoprotective agentsPhotoprotective agents: According to animal research, since PABA absorbs light primarily in the ultraviolet B spectrum, it may act synergistically with ultraviolet A absorbing agents in combination broad-spectrum sunscreen products (158).
  • PhotosensitizersPhotosensitizers: According to human research, PABA may act as a photocontact sensitizing agent (115; 116; 117). For this reason, its use in combination with other such agents potentially could result in a heightened phototoxic reaction.
  • PirenzipinePirenzipine: According to secondary sources, pirenzipine interferes with exocrine pancreatic function and decreases absorption of PABA, interfering with PABA test results. According to a case series evaluating the effectiveness of the PABA test, pirenzipine may decrease PABA serum levels (171).
  • Procaine-penicillinProcaine-penicillin: Case reports have suggested that there may be cross-sensitivity between PABA and procaine-penicillin, with worsening rash and possible development of autoimmunity in those patients exposed (148).
  • ProcainamideProcainamide: Since acetylation is the major route of metabolism for both PABA and procainamide, PABA may interfere with the biotransformation of procainamide to N-acetyl procainamide (NAPA), a potentially toxic metabolite. In one case series, PABA decreased biotransformation of procainamide into NAPA in patients who were rapid acetylators (172; 173). However, another study found that PABA impaired renal clearance of NAPA, but not of procainamide. Based on these findings, PABA does not appear to be useful for optimizing the safety and efficacy of procainamide (172).
  • Respiratory agentsRespiratory agents: In human research, withdrawals from study medication were reported due to adverse events that included secondary tuberculosis with an intravesical instillation of PAMBA and bacillus Calmette-Guerin (120).
  • SulfonamidesSulfonamides: Since sulfonamides function as PABA analogues that interfere with folic acid synthesis in bacteria, concurrent oral administration of PABA may decrease the effectiveness of sulfonamides (including sulfadiazine, sulfisoxazole, sulfamethoxazole, sulfamethizole, sulfasalazine, and co-trimoxazole) (174). Case reports have suggested that there may be cross-sensitivity between PABA and sulfonamides, with worsening rash and possible development of autoimmunity in those patients exposed (148).
  • TinidazoleTinidazole: According to one case series evaluating the usefulness of the UDCA-PABA (ursodeoxycholic acid-PABA) test in diagnosis of intestinal bacterial overgrowth, antibacterial treatment with tinidazole decreased urinary excretion of PABA in patients with bacterial overgrowth (46).
  • Topical drugsTopical drugs: According to animal research, PABA may penetrate the skin and attach to the stratum corneum via hydrogen bonding (158). In a clinical trial, padimate O, a PABA ester for topical use, enhanced transdermal estradiol delivery (166). According to these preliminary findings, it is plausible that this PABA derivative could enhance transdermal delivery of other topical agents as well.

    • PABA/Herb/Supplement Interactions:

  • AnestheticsAnesthetics: According to in vitro studies, butyl aminobenzoate (BAB) suspension may elicit long-lasting sensory (nonmotor) blockade when injected epidurally in patients with intractable pain (72; 161; 162). The safety of its use in combination with other anesthetic agents has not been well studied.
  • AnticoagulantsAnticoagulants: Based on a study in mice, intravenous administration of PABA may have anticoagulant activity (74; 119).
  • Antidiabetic agentsAntidiabetic agents: According to case reports, PABA may cause hypoglycemia (118).
  • AntihistaminesAntihistamines: According to case reports, there may be cross-sensitivity between PABA and certain antihistamines, with worsening rash and possible development of autoimmunity in those patients exposed (148).
  • Anti-inflammatoriesAnti-inflammatories: According to an animal study, PABA may have anti-inflammatory effects (75). However, PABA's interaction with other anti-inflammatory agents has yet to be determined.
  • AntioxidantsAntioxidants: According to an animal study, 4-aminobenzoic acid hydrazide (ABAH) may have antioxidant effects (175).
  • AntineoplasticsAntineoplastics: In animal research, administration of PABA delayed tumor induction in ultraviolet B irradiated mice (75). It is unclear how PABA may interact with other anti-tumor agents.
  • AntiviralsAntivirals: In human research, PABA appeared to exhibit antiviral synergistic effects when used with other medications, such as acyclovir, in the treatment of herpetic keratitis (53). Its use in combination with other antiviral herbs has not been well studied.
  • BronchodilatorsBronchodilators: According to a human study, PAMBA (para-aminomethylbenzoic acid) has been shown to reduce airway hyper-responsiveness following bronchoprovocation challenge in asthmatics (64). It is possible that it may act synergistically with other asthma medications, although there is no evidence to substantiate this hypothesis.
  • Cortisol-inducing or cortisol-suppressing agentsCortisol-inducing or cortisol-suppressing agents: According to anecdotal evidence, oral PABA may increase the effects and side effects of cortisone by decreasing its metabolism (165). Based on one small equivalence trial, PAMBA (para-aminomethylbenzoic acid) given intramuscularly to patients with pemphigus vulgaris may help minimize steroid requirements in these patients (58).
  • Cytotoxic agentsCytotoxic agents: Anecdotal evidence exists regarding PABA's ability to sensitize tumor cells to chemotherapy and radiation. One in vitro study also found that treatment of cells with para-aminobenzoic acid may reduce DNA breakage induced by chemical mutagens (82).
  • Dermatologic agentsDermatologic agents: Photocontact and contact sensitization (increased sensitivity of a patient's skin to light and chemicals) from PABA (115; 116; 117; 1; 149; 150; 136; 141; 147) and contact and photocontact dermatitis due to topical PABA derivatives (134; 16; 151; 138; 150) have been reported. Human research has also reported pruritus with use of PABA taken by mouth daily (65; 125).
  • Digestive enzymesDigestive enzymes: According to a case series, supplemental pancreatic enzymes may increase PABA absorption and recovery in patients undergoing the PABA test for pancreatic insufficiency (13).
  • Folic acidFolic acid: According to secondary sources, certain medications (i.e. sulfonamides, dapsone) function as PABA analogues, thereby inhibiting folic acid synthesis in sensitive micro-organisms. Folic acid supplementation in humans taking these medications may make these medications less effective by making this essential nutrient more available to bacteria.
  • Gastrointestinal agentsGastrointestinal agents: Gastrointestinal upset (57; 65; 124) including nausea and anorexia (125) from use of PABA has been reported in human research.
  • Gastrokinetic agentsGastrokinetic agents: According to a case series, gastrokinetic agents, such as domperidone, may correct for delayed gastric emptying in patients undergoing the PABA test for pancreatic insufficiency (169).
  • Genitourinary agentsGenitourinary agents: In human research, withdrawals from study medication were reported due to adverse events that included irritative symptoms (including urgency, frequency, or pain on urination) and hematuria with an intravesical instillation of PAMBA and bacillus Calmette-Guerin (120).
  • HematologicsHematologics: There have been several reports of methemoglobinemia (a condition in which ferrous iron [Fe2+] in hemoglobin gets oxidized to the ferric state [Fe3+], which results in altered oxygen affinity and impaired oxygen delivery to tissues) caused by topical or local anesthetics containing PABA derivatives (155; 156; 157). Transient leukopenia, particularly upon initiation of PABA treatment, has been noted in U.S. Pharmacopeia reports in 1999.
  • HepatotoxinsHepatotoxins: Jaundice (121) and abnormalities of liver function tests (122) have been noted in patients taking PABA, and hepatotoxicity has been reported from KPAB (potassium para-aminobenzoate) (118).
  • Hormonal agentsHormonal agents: According to a case study, padimate O (octyl dimethyl PABA) may function as a dermal penetration enhancer for systemic delivery of a topical estradiol spray (166).
  • HypoglycemicsHypoglycemics: According to case reports, PABA may cause hypoglycemia (118).
  • ImmunomodulatorsImmunomodulators: In patients with sensitivity to PABA, continued exposure to it may result in development of autoimmune diseases such as dermatomyositis and systemic lupus erythematosis, according to some case reports (148). Other human research has reported dropouts due to adverse events from PABA including fevers, chills, and cold sweats (65; 125; 120).
  • Neurologic agentsNeurologic agents: In human research, headaches from use of KPAB (57), and confusion, anxiety, and concentration difficulty from use of PABA (125) have been reported.
  • Photoprotective agentsPhotoprotective agents: According to animal research, since PABA absorbs light primarily in the ultraviolet B spectrum (158), it may act synergistically with ultraviolet A absorbing agents in combination broad-spectrum sunscreen products.
  • PhotosensitizersPhotosensitizers: According to human research, PABA may act as a photocontact sensitizing agent (115; 116; 117). For this reason, its use in combination with other such agents potentially could result in a heightened phototoxic reaction.
  • PhytoestrogensPhytoestrogens: According to a case study, padimate O (octyl dimethyl PABA) may function as a dermal penetration enhancer for systemic delivery of a topical estradiol spray (166).
  • ProbioticsProbiotics: According to a review, in the presence of para-aminobenzoic acid (PABA), Lactobacillus plantarum is capable of producing folate (176).
  • Respiratory agentsRespiratory agents: In human research, withdrawals from study medication were reported due to adverse events that included secondary tuberculosis with an intravesical instillation of PAMBA and bacillus Calmette-Guerin (120).
  • Topical agentsTopical agents: According to animal research, PABA may penetrate the skin and attach to the stratum corneum via hydrogen bonding (158). In a clinical trial, padimate O, a PABA ester for topical use, enhanced transdermal estradiol delivery (166). According to these preliminary findings, it is plausible that this PABA derivative could enhance transdermal delivery of other topical agents as well.

    • PABA/Food Interactions:

  • Oral absorptionOral absorption: According to a multicenter case series, differences in meal-time patterns may interfere with absorption of PABA (43).
  • Diabetic or hypoglycemic dietsDiabetic or hypoglycemic diets: According to case reports, PABA may cause hypoglycemia (118). For this reason, patients at risk for hypoglycemia may need to take PABA with meals.

    • PABA/Lab Interactions:

  • Bacterial overgrowthBacterial overgrowth: According to a human study, in the presence of bacterial overgrowth, PABA absorption and excretion increased (46).
  • Blood glucoseBlood glucose: According to case reports, PABA may cause hypoglycemia (118).
  • Coagulation panelCoagulation panel: According to a study in mice, intravenous administration of PABA may have anticoagulant activity (74; 119).
  • CortisolCortisol: According to anecdotal evidence, oral PABA may increase the effects and side effects of cortisone by decreasing its metabolism (165).
  • Liver function testsLiver function tests: According to human research, abnormalities of liver function tests have been noted in patients taking PABA (122).
  • PABA metabolites (PAHA, PAAHA)PABA metabolites (PAHA, PAAHA): According to human research, measurement of serum PABA metabolites following an oral loading dose of PABA may be useful in assessing liver function (47; 48; 49).
  • Pancreatic insufficiencyPancreatic insufficiency: According to human research, measurement of urinary PABA excretion following an oral loading dose appears to reflect pancreatic exocrine function (9; 10; 169; 12; 13; 14; 15; 16; 17; 18; 19; 20).
  • Renal insufficiencyRenal insufficiency: According to secondary sources, since PABA is primarily renally excreted, urinary PABA excretion may be reduced and serum PABA levels may be increased in patients with renal insufficiency following oral, intravenous, or intramuscular administration of PABA.
  • Respiratory function testsRespiratory function tests: According to a human study, PAMBA (para-aminomethylbenzoic acid) has been shown to reduce airway hyper-responsiveness following bronchoprovocation challenge in asthmatics (64). It is possible that it may act synergistically with other asthma medications, although there is no evidence to substantiate this hypothesis.
  • White blood cell countWhite blood cell count: U.S. Pharmacopeia reports from 1999 have noted that patients taking PABA may exhibit transient leukopenia upon initiation of treatment, which normalizes over time.